Sammelmappe1

BIOLOGICAL PSYCHOLOGY I

Giorgia Silani

giorgia.silani@sissa.it

STRUCTURE OF THE COURSE: WHEN

• Thursday 21/10/2010: 12 -17

• Friday 22/10/2010: 10-15

• Thursday 11/11/2010: 12 -17

• Friday 12/11/2010: 10-15

• Thursday 02/12/2010: 12 -17

• Friday 03/12/2010: 10-15

STRUCTURE OF THE COURSE: HOW

• 50 minutes: Frontal Lecture…but open to discussion.

•Feel free to ask questions!

• 10 minutes BREAK: you and me to recover a bit!

• After each topic, some practical exercise…good training for the final

exam

STRUCTURE OF THE COURSE: WHAT

• Chapter 01: Historical review .

• Chapter 02: Cell biology of neurons

• Chapter 03 - 04: Physiology of neural membrane

• Chapter 05 - 06: Communication between neurons

• Chapter 07: Anatomy of the nervous system

• Chapter 08: Smell and Taste

• Chapter 09 - 10: Visual system

• Chapter 11: Auditory system

• Chapter 12: Somatic sensory system

• Chapter 13 - 14: Motor systems

Textbook: Bear, Connors, Paradiso “Neuroscience,

exploring the brain – 3rd edition”

Additional material on the webpage of the course

Take home message…a lot of stuff to do.

Torino, Italy Milano, Italy London, UK

Zurich, Switzerland

STRUCTURE OF THE COURSE: WHO

Trieste, Italy

LET’S START

NEUROSCIENCE:

PAST, PRESENT, AND FUTURE

THE ORIGINS OF NEUROSCIENCE

Neuroscience is the scientific study of the nervous

system.

Relatively young term (Society for Neuroscience 1969)

..but curiosity about the brain and how it works is old as

much as the mankind itself

7000 B.C. ... long time ago

• Prehistoric ancestors

– Brain vital to life

• Skull surgeries

– Evidence: Trepanation

– Skulls show signs of healing

5000 B.C. ... Ancient Egypt

Heart: Seat of soul and memory (not the head)

Mummification process

Canopic Jars were used to hold the organs of the dead after they were

embalmed.

The four organs housed by the jars were the lungs, the stomach, the liver

and the intestines.

Egyptians held no regard for the brain, which was discarded.

The heart (scarab) was left inside the body, to be judged in the afterlife

500 B.C. ... Ancient Greece

Hippocrates (460 -379 B.C.)

• Brain: Involved in sensation;

• Seat of intelligence

Aristotle (384 -322 B.C.)

• Heart: centre of intellect;

• Brain: Radiator for the cooling

of the blood

A.D. ... Roman Empire

Galen (130 -200 A.D.)

Correlation between structure and function

• Cerebrum: soft = sensations

• Cerebellum: hard= movements

• Ventricles: contains fluids which

movements to or from regulate perception

and actions

From Reinassance to the XIX Century

The Renaissance

Fluid-mechanical theory of brain function

Philosophical mind-brain distinction

Descartes (1596-1650)

The Seventeenth and Eighteenth Centuries

Gray matter and white matter observation

Basic anatomical subdivisions of PNS and CNS

Identifications of gyri, sulci, and fissures

Beginning of the Nineteenth Century

Nerve as wires, understanding of electrical phenomena,

brain can generate electricity

Studies of Charles Bell and Francois Magendie on ventral

and dorsal roots of the nerves

the XIX Century

.

Localization of Function in the Brain

If spinal roots carry differential functional information then

different parts of the brain are specialized to process this

information

1823 - Experimental ablation method

Marie-Jean-Pierre Flourens

1809 - Phrenology

Franz Joseph Gall

1861 – Lesioned patients

Paul Broca

the XIX Century

Cerebral localization in animals

Nervous systems of different

species may share common

mechanisms

Neuron as the basic

function of the brain

Neuroscience today

Levels of Analysis

Molecular (i.e. neurotransmitter, enzymes etc.)

Cellular (i.e. types of neurons and their properties)

Systems (i.e. visual, auditory etc.)

Behavioral (from networks to behaviors)

Cognitive ( from brain to mind, i.e. consciousness)

Neuroscientists

The cost of ignorance

NEURONS AND GLIA

CELLS IN THE NERVOUS SYSTEM

Neurons Process information Sense environmental changes Communicate changes to other neurons Command body response

Glia Insulates, supports, and nourishes neurons

THE NEURON DOCTRINE

Cells are in the range of 0.01 – 0.05 mm of diameter

Need for techniques that allow to see such small structures

Histology

Microscopic study of tissue structure

The Nissl Stain (late XIX century)

Colors selectively only part of the cell (Nissl body)

Facilitates the study of cytoarchitecture in the CNS

Differentiation between neuron and glia

The Golgi Stain (1873)

Revealed the entire structure of the neuron

THE NEURON DOCTRINE

THE NEURON DOCTRINE

Santiago Ramon y Cajal’s neuron doctrine

Neuron are not continuous one another but communicate by contact

Camillo Golgi’s reticular theory

Neurites of different cells are fused together to form a continuous reticulum, a

network (like blood circulation)

Shared the 1906 Nobel Prize in

Physiology or Medicine

THE NEURON

Neuronal membrane

separate the inside from the outside

The Soma

Cytosol: Watery fluid inside the cell

Organelles: Membrane-enclosed

structures within the soma

Nucleus

Rough Endoplasmatic Reticulum,

Smooth Endoplasmatic Reticulum,

Golgi Apparatus

Mitochondria

Cytoplasm: Contents within a cell

membrane (e.g., organelles, excluding

the nucleus)

THE NUCLEUS

Contains chromosomes that have the

genetic material (DNA)

Genes: segment of DNA

Gene expression: reading of DNA in order

to synthesize proteins

Protein synthesis happen in the cytoplasm

RNA is the messenger that carry the

information contained in the DNA to the

cytoplasm

THE NUCLEUS

The enzyme RNA polymerase binds to the promoter of the gene in order to initiate

transcription

Exons: coding regions

Introns: non –coding regions

In the cytoplasm mRNA transcript

is used to assemble proteins

from amino acids

DNA

transcription

Proteins

mRNA

translation

ROUGH ENDOPLASMATIC RETICULUM

Major site for protein synthesis

Contains ribosomes attached to the

ER and free ribosomes

Cytosol Membrane

SMOOTH ER and GOLGI APPARATUS

Sites for preparing/sorting proteins for delivery to different cell regions (trafficking)

and regulating substances

THE MITOCHONDRION

Site of cellular respiration (inhale and

exhale)

Pyruvic acid and O2, trough the Krebs

cycle are transformed in ATP and CO2

1 Pyruvic acid = 17 ATP

ATP- cell’s energy source (by breakdown

of ATP in ADP)

THE NEURONAL MEMBRANE

Barrier that encloses cytoplasm

~5 nm thick

Protein concentration in membrane varies

Structure of discrete membrane regions influences neuronal

function

THE CYTOSKELETON

Not static

Internal scaffolding of neuronal membrane

Three “bones”

Microtubules

Microfilaments

Neurofilaments

Microtubules

Big and run longitudinally along the neuron.

Microfilaments

Same size of the membrane. Role in changing cell

shape

Neurofilaments

Mediam size. Structurally very strong

THE AXON

The Axon is specialized for the transfer

information over long distances Axon hillock (beginning)

Axon proper (middle)

Axon terminal (end)

Differences between axon and soma ER does not extend into axon

(This means no protein synthesis there)

Protein composition: Unique

Variable diameter and length

THE SYNAPSE

The axon terminal is the site of contact with

another neuron or cell (synapse) and

transfer of information (synaptic

transmission)

In the Axon Terminal there are no

microtubules

Presence of synaptic vesicles (contain

neurotransmitter)

Abundance of membrane proteins post

synapsis)

Large number of mitochondria

THE AXOPLASMIC TRANSPORT

Allows the transport of the proteins

synthesized in the soma to the axon

terminal

Anterograde (soma to terminal):

could be fast (1000mm per day) or

slow (1-10 mm per day). Legs are

Kinesin

Retrograde (terminal to soma)

transport: feedback information.

Legs are dynein

THE DENDRITE

“Antennae” of neurons

All the dendrites of a neuron are called dendritic tree

Dendritic spines

Postsynaptic: receives signals from axon terminal by using protein

molecules called receptors that detect neurotransmitters in the synaptic

cleft

CLASSIFICATION OF NEURONS

Classification Based on Dendritic and Somatic Morphologies

Stellate cells (star-shaped) and pyramidal cells (pyramid-

shaped)

Spiny or aspinous

Classification Based on the Number of Neurites

Single neurite

Unipolar

Two or more neurites

Bipolar- two

Multipolar- more than two

CLASSIFICATION OF NEURONS

Further Classification

By connections within the CNS

Primary sensory neurons, motor neurons, interneurons

Based on axonal length

Golgi Type I - long axon, projection neurons

Golgi Type II - short axon, local circuit neurons

Based on neurotransmitter type

e.g., – Cholinergic = Acetycholine at synapses

GLIA

Mainly supports neuronal functions

Myelinating Glia Oligodendroglia (in CNS) and Schwann

cells (in PNS) insulate axons

Node of Ranvier: region where the

axonal membrane is exposed

Astrocytes Most numerous glia in the brain

Fill spaces between neurons (Influence

neurite growth)

Regulate the chemical context of the

external environment of the neurons

THE NEURAL MEMBRANE

AT REST

ELECTRICAL PROPERTIES

Simple reflex : information needs to be quickly transmitted to the CNS and back Information is transmitted through action potentials (change in the electrical properties of the membrane)

Cells able to generate an AP have excitable membrane At rest, these cells have a inside negative electrical charge (resting membrane potential) that become positive during the AP

CYTOSOLIC AND EXTRACELLULAR FLUID

Water is the key ingredient in intracellular and extracellular fluid

Key feature – uneven distribution of electrical charge (O has a net negative

charge)

Ions are atoms or molecules with a net electrical charge dissolved in the water

Salz for example is a crystal of Sodium (Na+) and Chloride (Cl-)

Monovalent Ion: Difference between protons and electrons =1,

Divalent Ion: Difference between protons and electrons =2,

cation (+), anion (-)

When the crystal breaks down spheres of

hydration -layer of water are attracted to the ion

The orientation of the water molecules is

determined by the valence of the ion

IONS INVOLVED IN CELLULAR PHYSIOLOGY

Sodium

Potassium

+

+

Calcium

Chloride

2+

-

THE PHOSPHOLIPID MEMBRANE

Hydrophilic: Dissolve in water due to uneven electrical charge (e.g., salt,

proteins, carbohydrates)

Hydrophobic: Does not dissolve in water due to even electrical charge (e.g., oil,

lipids in general)

The Phospholipid Bilayer

Hydrophilic

Hydrophobic

Resting and Action potentials depend on special proteins that are inserted in the

membrane

THE PROTEIN

Proteins are molecules assembled by combination of different amino acids (20 types)

Central alpha

carbon

R group

Amino group Carboxyl group

THE PROTEIN STRUCTURE

Primary

Secondary

Tertiary

Quaternary

Peptide bond

CHANNEL PROTEINS

Ion Channels

They form a pore through the membrane that

is ion selective

They can be opened and closed (gated)

by changing in the local microenvironment

of the membrane

hydrophilic

hydrophobic

Ion Pumps

Formed by membrane spanning proteins

Uses energy from ATP breakdown

Neuronal signaling

THE MOVEMENT OF IONS

Diffusion: movement of ion due to concentration levels Dissolved ions tend to distribute evenly by following down concentration gradient Concentration gradient = difference of concentration of an ion across the membrane

Electricity Electrical current (I, measured in Amperes) represents ion movement.

It’s regulated by

1) electrical conductance (g, measured in Siemens) or electrical

resistance (R, measured in Ω): ability (or inability) of an electrical

charge to migrate from one point to another

2) electrical potential (V, measured in volts): difference in charge

between cathode and anode

THE MOVEMENT OF IONS

Electrical current flows across the membrane by

Ohm’s law relationship

I =gV or I =V/R

Membrane potential: Voltage across the

neuronal membrane.

The resting potential is typically -65 mV

…let’ see why…

EQUILIBRIUM POTENTIAL

Example 1

Example 2

Equilibrium is reached when

diffusional and electrical

forces are equal and opposite

(equilibrium potential, Eion)

MEMBRANE POTENTIAL

In the membrane ions have different concentration between inside and outside,

and this gradient is established by action of ionic pumps, that use energy in

order to move ions against concentration forces

Membrane permeability determines membrane resting and action potentials

MEMBRANE POTENTIAL

Membrane permeability determines membrane resting and action potentials

Membrane rest potential is determined by the higher number of K vs. Na channels

open (resting potential close to Ek potential)

THE ACTION POTENTIAL

ACTION POTENTIAL

Conveys information over distance in the nervous system Rapid reversal of the membrane potential at rest

ACTION POTENTIAL

The Generation of an Action Potential is caused by depolarization of the

membrane beyond threshold

“All-or-none” event

Chain reaction

e.g., Puncture foot, stretch membrane of nerve fibers

Opens Na+-permeable channels Na+ influx depolarized

Membrane reaches threshold action potential

ACTION POTENTIAL

A way to study the properties of AP is the Generation of Multiple Action Potentials

Artificially - inject current into a neuron using a microelectrode

ACTION POTENTIAL

Firing frequency reflects the magnitude of the depolarizing current

The maximum firing frequency is 1000 Hz. This means that after an AP, is not

possible to initiate another one for at least 1 msec (absolute refractory period).

Also the initiation of another AP after few msec requires more current

(relative refractory period).

THE ACTION POTENTIAL IN THEORY

If only K+ channel are open then the membrane would reach EK+

THE ACTION POTENTIAL IN THEORY

But if the membrane is also permeable to Na+ , the EP will go towards ENa+

Rising phase (depolarization):

Inward sodium current

Falling phase (repolarization):

Outward potassium current

THE ACTION POTENTIAL IN REALITY

First described by Hodgkin and Huxley, with the use of a voltage Clamp: “Clamp”

membrane potential at any chosen value

Rising phase transient increase in gNa, influx of Na+ ions

Falling phase increase in gK, efflux of K+ ions

Existence of sodium “gates” in the axonal membrane sensitive to change

in membrane potential and selective for Na

THE ACTION POTENTIAL IN REALITY

The Voltage-Gated Sodium Channel

1) sensitivity to change in membrane potential

2) selectivity for Na

THE ACTION POTENTIAL IN REALITY

The Voltage-Gated Sodium Channel

Open with little delay

Stay open for about 1msec

Cannot be open again by

depolarization (Absolute

refractory period: Channels

are inactivated)

THE ACTION POTENTIAL IN REALITY

The Voltage-Gated Potassium Channels

Open in response to depolarization but later than sodium gates

Potassium conductance serves to rectify or reset membrane potential

(Delayed rectifier)

Structure: Four separate polypeptide subunits join to form a pore

THE ACTION POTENTIAL IN REALITY

To summarize- Key Properties of the Action

Potential are

•Threshold

•Rising phase

•Overshoot

•Falling phase

•Undershoot

•Absolute refractory period

•Relative refractory period

THE ACTION POTENTIAL CONDUCTION

Down axon to the axon terminal

Orthodromic: Action potential travels in one direction

Antidromic (experimental): Backward propagation

Typical conduction velocity: 10 m/sec and length of action potential: 2 msec

THE ACTION POTENTIAL CONDUCTION

Factors Influencing Conduction Velocity:

1) Spread of action potential along membrane follows the path of less

resistance. It depends upon axon structure and direction of positive

charge

2) Path of the positive charge

Inside of the axon (faster)

Across the axonal membrane (slower)

3) Axonal excitability

Axonal diameter (bigger = faster)

Number of voltage-gated channels opens

THE ACTION POTENTIAL CONDUCTION

Layers of myelin sheath facilitates current flow (saltatory conduction)

Myelinating cells

1) Schwann cells in the PNS

2) Oligodendroglia in CNS

THE ACTION POTENTIAL CONDUCTION

Saltatory conduction

0.2 - 2 mm

THE ACTION POTENTIAL INITIATION

SYNAPTIC TRANSMISSION

SYNAPTIC TRANSMISSION

1897: Charles Sherrington- “synapse”

The process of information transfer at a synapse

Plays role in all the operations of the nervous system

Information flows in one direction: Neuron to target cell

First neuron = Presynaptic neuron

Target cell = Postsynaptic neuron

Types of synapses:

1) Chemical (1921- Otto Loewi)

2) Electrical (1959- Furshpan and

Potter)

ELECTRICAL SYNAPSES

Gap junction

Cells are said to be “electrically coupled”

Flow of ions from cytoplasm to cytoplasm

and in both directions

Transmission is fast

ELECTRICAL SYNAPSES

An AP in the pre synaptic cell, generate a PSP (post synaptic potential) in the

post synaptic cell

If several PSPs occur simultaneously to excite a neuron this generates an AP

(Synaptic integration)

CHEMICAL SYNAPSES

Key elements:

Synaptic cleft (wider the gap junction);

Presynaptic element (usually an axon terminal )

Synaptic vesicles (storage of neurotransmitter)

Secretory granules (bigger vesicles)

Postsynaptic density (receptor that converts chemical signal

into electrical signal )

Postsynaptic cell

CNS SYNAPSES

Axodendritic: Axon to dendrite

Axosomatic: Axon to cell body

Axoaxonic: Axon to axon

Dendrodendritic: Dendrite to dendrite

Gray’s Type I: Asymmetrical,

excitatory

Gray’s Type II: Symmetrical,

inhibitory

NEUROMUSCULAR JUNCTION

Synaptic junction outside the CNS Studies of NMJ established principles of synaptic transmission One of the largest and faster synapses in the body

PRINCIPLES OF CHEMICAL SYNAPTIC

TRANSMISSION

Basic Steps

• Neurotransmitter synthesis

• Load neurotransmitter into synaptic vesicles

• Vesicles fuse to presynaptic terminal

• Neurotransmitter spills into synaptic cleft

• Binds to postsynaptic receptors

• Biochemical/Electrical response elicited in postsynaptic cell

• Removal of neurotransmitter from synaptic cleft

PRINCIPLES OF CHEMICAL SYNAPTIC

TRANSMISSION

Neurotransmitters

Amino acids: Small organic molecules

stored in and released from synaptic

vesicles (Glutamate, Glycine, GABA)

Amines: Small organic molecules stored

in and released from synaptic vesicles

(Dopamine, Acetylcholine, Histamine)

Peptides: Short amino acid chains (i.e.

proteins) stored in and released from

secretory granules (Dynorphin,

Enkephalins)

PRINCIPLES OF CHEMICAL SYNAPTIC

TRANSMISSION

Neurotransmitter Synthesis and Storage A part from amino acids, amines and peptides are synthesized from precursors only in neuron

that release them.

Amine and amino acids are synthesized in the axon terminal and the take up by the vesicles

with the help of the transportes .

Peptides are synthesized in the rough ER, eventually split in the Golgi apparatus and then

carried to the axon terminal in the secretory granules

PRINCIPLES OF CHEMICAL SYNAPTIC

TRANSMISSION

Neurotransmitter release by exocytosis AP opens voltage gate calcium channel

Process of exocytosis stimulated by release of intracellular calcium, [Ca2+]I, due to the AP.

Vesicle membrane fuses into presynaptic membrane with subsequent release of neurotransmitter

Vesicle membrane recovered by endocytosis and then refilled with new neurotransmitter

PRINCIPLES OF CHEMICAL SYNAPTIC

TRANSMISSION

Neurotransmitter Receptors and Effectors (postsynaptic cell)

Ionotropic: Transmitter-gated ion channels Metabotropic: G-protein-coupled receptor

Autoreceptors: Presynaptic receptors sensitive to neurotransmitter released by presynaptic

terminal. Act as safety valve to reduce release when levels are high in synaptic cleft

(autoregulation)

PRINCIPLES OF CHEMICAL SYNAPTIC

TRANSMISSION

IPSP: Transient hyperpolarization

of postsynaptic membrane

potential caused by presynaptic

release of neurotransmitter

EPSP: Transient postsynaptic

membrane depolarization by

presynaptic release of

neurotransmitter

PRINCIPLES OF CHEMICAL SYNAPTIC

TRANSMISSION

Neurotransmitter Recovery and Degradation Neurotransmitter must be cleared from the synaptic cleft. Different ways.

Diffusion: Away from the synapse

Reuptake: Neurotransmitter re-enters presynaptic axon terminal

Enzymatic destruction inside terminal cytosol or synaptic cleft

Desensitization: e.g., AChE cleaves Ach to inactive state

PRINCIPLES OF SYNAPTIC INTEGRATION

Synaptic Integration

Process by which multiple synaptic potentials combine within one postsynaptic

neuron

PRINCIPLES OF SYNAPTIC INTEGRATION

Quantal Analysis of EPSPs The synaptic vesicle is the elementary units of synaptic transmission The amplitude of an EPSP is some multiple of the response to the content of a vesicle (quantum) Quantal analysis is used to determine number of vesicles that release during neurotransmission Miniature postsynaptic potential (“mini”) are normally generated spontaneously

PRINCIPLES OF SYNAPTIC INTEGRATION

EPSP Summation Allows for neurons to perform sophisticated computations. EPSPs are added together to

produce significant postsynaptic depolarization. Two types:

Spatial: EPSP generated simultaneously in different spaces

Temporal: EPSP generated at same synapse in rapid succession

PRINCIPLES OF SYNAPTIC INTEGRATION

Inhibition Action of synapses to take membrane potential away from action potential threshold

IPSPs and Shunting Inhibition Excitatory vs. inhibitory synapses: Bind

different neurotransmitters (GABA or Glycine),

allow different ions to pass through channels

(Chloride, Cl-)

Membrane potential less negative than -65mV

= hyperpolarizing IPSP

Shunting Inhibition: Inhibiting current flow from

soma to axon hillock

PRINCIPLES OF SYNAPTIC INTEGRATION

The Geometry of Excitatory and Inhibitory Synapses

Excitatory synapses (Glutamate) usually have Gray’s type I morphology

Clustered on soma and near axon hillock

Inhibitory synapses (GABA, Glycine) have Gray’s type II morphology

Gray’s Type I: Asymmetrical, excitatory

Gray’s Type II: Symmetrical, inhibitory

PRINCIPLES OF SYNAPTIC INTEGRATION

Modulation

Synaptic transmission that modifies effectiveness of EPSPs generated by other

synapses with transmitter-gated ion channels

Example: Activating NE β receptor

NEUROTRANSMITTER SYSTEMS

NEUROTRANSMITTER

Basic criteria:

1. The molecule must be synthetized and stored in the presynaptic neuron

2. The molecule must be released by the presynaptic axon terminal upon

stimulation

3. The molecule, when experimentally applied, must produce a response in the

postsynaptic cell that mimics the response generated by the release of the

neurotransmitter by the presynaptic cell

HOW TO STUDY NEUROTRASMITTERS

Localization of Transmitters and Transmitter-synthesizing enzyme

Immunocytochemistry

Anatomically localize particular molecules to particular cells

HOW TO STUDY NEUROTRASMITTERS

Studying Transmitter Localization

In situ hybridization

mRNA strands can be detected by complementary probe

Probe can be radioactively labeled - autoradiography

HOW TO STUDY NEUROTRASMITTERS

Studying Transmitter Release

Loewi and Dale identified Ach as a transmitter

CNS contains a diverse mixture of synapses that use different

neurotransmitters

impossible to stimulate a single population of synapses

Brain slice as a model (ex vivo, brain in a dish)

Kept alive in vitro Stimulate synapses, collect and measure

released chemicals (mixture)

Often stimulated by high K+ solution to cause massive synaptic release

Ca2+ dependency of the release has to be confirmed

HOW TO STUDY NEUROTRASMITTERS

Studying Receptors

No two transmitters bind to the same receptor; however one neurotransmitter

can bind to many different receptors

Receptor subtypes

Neuropharmacology

Subtype specific agonists and antagonists

ACh receptors

Skeletal muscle Heart

HOW TO STUDY NEUROTRASMITTERS

Studying Receptors

HOW TO STUDY NEUROTRASMITTERS

Studying Receptors

Ligand-binding methods

Drugs that interact selectively with neurotransmitter receptors were used

to analyze natural receptors

Solomon Snyder and opiates

Identified receptors in brain

Subsequently found endogenous opiates

Endorphins, dynorphins, enkephalins

Enormously important for mapping the anatomical distribution of different

neurotransmitter receptors in brain

NEUROTRASMITTER CHEMISTRY

Cholinergic (ACh) Neurons

good marker for cholinergic neurons

Rate-limiting step of

Ach synthesis

Secreted from the axon

terminal and associated with

axon terminal membrane

NEUROTRASMITTER CHEMISTRY

Cholinergic (ACh) Neurons Cholinergic (ACh) Neurons

Synthesis

Degradation

NEUROTRASMITTER CHEMISTRY

Catecholaminergic Neurons

Involved in movement, mood, attention,

and visceral function

Tyrosine: Precursor for three amine

neurotransmitters that contain catechol

group

Dopamine (DA)

Norepinephrine (NE, noradrenaline)

Epinephrine (E, adrenaline)

Marker for catecholaminergic neurons

Rate limiting, regulated by

physiological signals •Low-rate release - increased

catecholamine conc. - inhibit TH activity

•High-rate release - increased Ca2+ influx

- boost TH activity

Present in the synaptic vesicles

Present in the cytosol

Released from the adrenal gland as well

NEUROTRASMITTER CHEMISTRY

• Serotonergic Neurons

– Serotonin (5-HT,5-

hydroxytryptamine) is derived

from tryptophan

– Regulates mood, emotional

behavior, sleep

– Synthesis of serotonin

• Limited by the availability of

blood tryptophan (diet)

– Selective serotonin reuptake

inhibitors (SSRIs):

Antidepressants

NEUROTRASMITTER CHEMISTRY

• Amino Acidergic Neurons

– Amino acid neurotransmitters: Glutamate, glycine, gamma-aminobutyric acid (GABA)

– Glutamate and glycine

• Present in all cells - Differences among neurons are quantitative NOT qualitative

• Vesicular transporters are specific to these neurons

– Glutamic acid decarboxylase (GAD)

• Key enzyme in GABA synthesis

• Good marker for GABAergic neurons

• One chemical step difference between major excitatory transmitter and major inhibitory transmitter

NEUROTRASMITTER CHEMISTRY

THE CENTRAL NERVOUS SYSTEM

ANATOMICAL REFERENCES

Rostral/Anterior

Caudal/Posterior

Dorsal

Ventral

Rostral/Anterior

Caudal/PosteriorMedialLateral

MedialLateral

AXIAL

CORONAL

SAGITTAL

THE MENINGES

Insula

space

space

membrane

Artery

Brain

The meninges are filled with cerebrospinal fluid (CSF)

Whole Brain GM WM CSF

THE CNS

Cerebrum

BrainstemCerebellum

MAJOR SULCILongitudinal sulcus

MAJOR SULCICentral sulcus

Lateral (sylvian) fissure

CEREBRAL LOBESParietal

Temporal

Frontal

Occipital

CEREBRAL LOBES

Insula

CEREBELLUM

InsulaVermis

Left Cerebellar Hemisphere Right Cerebellar Hemisphere

WHITE MATTER TRACTS

InsulaVermis

Left Cerebellar Hemisphere Right Cerebellar Hemisphere

FUNCTIONAL CLASSIFICATION

BROADMANN’S CLASSIFICATION

Insula

THE CNS

Insula

Thalamus

Hypothalamus

Pineal body

Midbrain

Tegment

Tectum

Pons

Medulla

Cerebellum

Diencephalon

Telencephalon

THE VENTRICULAR SYSTEM

Insula

Lateral ventricles

thirdventricle

fourthventricle

Third ventricle

Fourth ventricle

Fourth ventricle

Fourth ventricle

Lateral ventriclesFourth ventricle

THALAMIC NUCLEI

Insula

CEREBRAL CIRCULATION

Insula

Anterior Cerebral Artery

Anterior Communicating Artery

Middle Cerebral Artery

Internal Carotid Artery

Basilar Artery

Posterior Communicating Artery

Posterior Cerebral Artery

Superior CerebellarArtery

Vertebral Arteries

CEREBRAL CIRCULATION

Insula

Terminal branches of Anterior Cerebral Artery

Middle Cerebral Artery Terminal branches of Posterior Cerebral Artery

CEREBRAL CIRCULATION

Insula

Anterior Cerebral Artery

Posterior Communicating Artery

Posterior Cerebral Artery

CEREBRAL CIRCULATION

Insula

Anterior Cerebral Artery

Posterior Cerebral Artery

Surface branches supply cortex and white matter of :1)inferior frontal lobe2)medial surface of the frontal and parietal lobes3)anterior corpus callosum

Surface branches supply cortex and white matter of: 1)medial occipital lobes2)inferior temporal lobes3)posterior corpus callosum

Middle Cerebral Artery

Surface branches supply cortex and white matter of: hemispheric convexity (all four lobes and insula).

CEREBRAL CIRCULATION

Middle Cerebral Artery Stroke

Most common stroke syndrome. Symptoms: -contralateral weakness (face, arm, and hand more than legs)-contralateral sensory loss (face, arm, and hand more than legs) -visual field cut (damage to optic radiations) -aphasia: language disturbances (more likely with L. Hemi. Damage)-impaired spatial perception (more likely after R. Hemi. Damage)

Insula

CEREBRAL CIRCULATION

Anterior Cerebral Artery

Posterior Cerebral Artery

- Motor disturbance contralateral distal leg - urinary incontinence- speech disturbance (may be more of a motor problem) - apraxia of left arm (sympathetic apraxia) if anterior corpus callosum is affected- if bilateral may cause apathy, motor inertia, and muteness

Visual disturbances:-contralateral homonymous hemianopsia (central vision is often spared) -L. Hemi: lesions alexia (with or without agraphia) -Bilateral lesions: cortical blindness : patients unaware they cannot see -Memory impairment if temporal lobe is affected

Insula

CRANIAL NERVES

InsulaPosterior Communicating Artery

THE CHEMICAL SENSES

THE CHEMICAL SENSES

Animals depend on the chemical senses to identify nourishment

Chemical sensationOldest and most common sensory system with the aim to detect environmental chemicals

Chemical sensesGustation & Olfaction (separate but processed in parallel)Chemoreceptors

TASTE

The Basics TastesSaltiness, sourness, sweetness, bitterness, and umami.

Innate preferences and rejections for particular tastes (sweet and bitter) have a survival reasons

Usually there is correspondence between chemical ingredients andtaste:

Sweet—sugars like fructose, sucrose, artificial sweeteners (saccharin and aspartame)Bitter—ions like K+ and Mg2+, quinine, and caffeineSalty—saltsSour—acids

How to distinguish the countless unique flavors of a food1) Each food activates a different combination of taste receptors2) Distinctive smell (it combines with taste to give the flavor)3) Other sensory modalities (texture and temperature)

TASTE

The Organs of TasteTongue, mouth, palate, pharynx, and epiglottisNasal cavity for smell

TASTEAreas of sensitivity on the tongue (but most of the tongue is sensitive to all basics tastes)

Tip of the tongue: SweetnessBack of the tongue : BitternessSides of tongues: Saltiness and sourness

Papillae (taste receptors)FoliateVallateFungiform

At threshold concentration (just enough exposure of single papilla to detect taste) they respond to only one taste. More concentrations lead to less selectivity

TASTETastes Receptor Cells

Apical end is the chemically sensitive part. It has small extensions called microvillithat project into the taste pore.Receptor potential: Voltage shift – depolarization of the membrane cause CA++ entering the cell and release of transmitter

TASTE

Transduction: process by an environmental stimulus cause an electrical response in a sensory receptor.

In the case of taste, chemical stimuli (tastants) may:

1)Pass directly through ion channels2)Bind to and block ion channels3)Bind to G-protein-coupled receptors

Slightly different mechanisms for saltiness, sourness, bitterness, sweetness and umami (amino acids)

TASTE

SournessSourness- acidity – low pHH + binds to and block ion channelscausing deporalization

SaltinessSpecial Na+ selective channel. The ion pass directly through channelcausing deporalization

TASTE

BitternessBitter substances are detected by different types T1R and T2R receptor. They work as G-protein coupled receptors

SweetnessIt also detected by receptors T1R2+T1R that have the same signaling mechanism (cf. bitter taste)The expressed in different taste cells allow the system not to be confused about the taste

UmamiUmami receptors T1R1+T1R3 detect amino acids

TASTE

Bitterness Sweetness Umami

TASTE

VII Facial nerveIX Glossopharyngeal nerveX Vagus nerveThey carry primary gustatory axons

Gustatory nucleusPoint where taste axons bundle and synapse

Ventral posterior medial nucleus (VPM)Deals with sensory information from the head

Primary gustatory cortex (Insula)Receives axons from VPM taste neurons

Lesion in VPM and Gustatory cortex can cause ageusia- the loss of taste perception

SMELL

Smell is not only important for taste but also for social communication

Pheromones are important signals• Reproductive behavior• Territorial boundaries• Identification• Aggression

SMELL

The Organs of Smell1)Olfactory epithelium: contains olfactory receptor cells, supporting cells (produce mucus), and basal cells (source of new receptor cells)2)Olfactory axons constitute olfactory nerve3)Cribriform plate: A thin sheet of bone through which small clusters of axons penetrate, coursing to the olfactory bulb

Anosmia: Inability to smell

SMELL

Olfactory Transduction

Receptor potential: if strong enough generates APs in the cell body and spikes will propagate along the axon

SMELL

Adaptation: decreased response despite continuous stimulus. Common features of sensory receptors across modalities

Each receptor cell express a single olfactory receptor protein.

They responds to different odours but with preferences.

Many different cells are scattered into the epithelium

SMELL

Central Olfactory Pathways

Mapping of receptor cell into glomeruli is extremely precise

SMELL

Axons of the olfactory tract branch and enter the forebrain (unconscious perception) bypassing the thalamus

Neocortex (conscious perception) is reached by a pathway that synapses in the medial dorsal nucleus of the thalamus

THE EYE

LIGHTVision is probably the most important sense in humans and animals. This system works by transducing the property of light into a complex visual percept

Light is an electromagnetic radiation visible to the eye. It’s defined by 3 parameters: wavelength (distance btw two peaks or troughs)frequency (number of waves per second)amplitude (difference btw wave trough and peak)

The energy content of a radiation is proportional to his frequency.Only a small part of the electromagnetic spectrum is visible to our eyes

LIGHTOptics is the study of light rays and their interactions

Reflection: bouncing of light rays off a surfaceAbsorption: transfer of light energy to a particle or surfaceRefraction: changing of a direction due to change in speed of light rays, due to the passing from one medium to another

ANATOMY OF THE EYE

Pupil: Opening where light enters the eye

Sclera: White of the eye

Iris: Gives color to eyes. Contains 2 muscles that give size to the pupil

Cornea: Glassy transparent external surface of the eye

Extraocular muscles: move the eyeball in the orbit

Optic nerve: Bundle of axons from the retina

THE RETINA

Optic disk: where blood vessels originate and axons leave the retina

Macula: part of retina for central vision

Fovea: marks the center of the retina

CROSS SECTION OF THE EYECiliary muscles: Ligaments that suspend lensLens: Change shape to adjust focus. It divides eyes into two compartments:1) anterior chamber containing aqueous humor 2) posterior chamber containing vitreous humor

lens

iris

light

cornea

aqueous humor

ciliary muscles

scleravitreous humor

optic nerve

fovea

retinazonule fibers

IMAGE FORMATION

Eye collects light, focuses on retina, forms images.The cornea is the site of most of the refractive power of the eye

Focal distance: from refractive surface to the point where the rays converges. Depends on the curvature of the cornea

IMAGE FORMATION

Accommodation by the LensChanging shape of lens allows for extra focusing power

IMAGE FORMATION

IMAGE FORMATION

The Pupillary Light ReflexDepends on connections between retina and brain stem neurons that control muscle around pupil and aim to continuously adjust to different ambient light levels. It is consensual for both eyes

The Visual FieldAmount of space viewed by the retina when the eye is fixated straight ahead

Visual AcuityAbility to distinguish two nearby pointsVisual Angle: Distances across the retina described in degrees

MICROSCOPIC ANATOMY OF THE RETINAPhotoreceptors: cells that convert light energy into neural activity

In the Retina cells are organized in layers . Inside-out

MICROSCOPIC ANATOMY OF THE RETINA

Photoreceptor StructureTransduction of electromagnetic radiation to neural signals

Four main regions1) Outer segment2) Inner segment3) Cell body4) Synaptic terminal

Types of photoreceptorsRods (scotopic vision-dark) and cones (photopic vision-light)

MICROSCOPIC ANATOMY OF THE RETINA

Regional Differences in Retinal StructureVaries from fovea to retinal periphery

In peripheral retina there is higher ratio of rods to cones, and higher ratio of photoreceptors to ganglion cells resulting in more sensitive to light

In the fovea (pit in retina) visual acuity is maximal. In Central fovea there are only cones (no rods) and 1:1 ratio with ganglion cells

PHOTOTRANSDUCTION

Phototransduction in RodsDepolarization in the dark: “Dark current” and hyperpolarization in the lightOne opsin in rods: Rhodopsin

Receptor protein that is activated by light

G-protein receptor Photopigment

PHOTOTRANSDUCTION

Depolarization in the dark: “Dark current” and hyperpolarization in the light:Constant inward sodium current

Light activate an enzime that destroy the cGMP, causing the closing of Na+ channel

PHOTOTRANSDUCTION

PHOTOTRANSDUCTION

Phototransduction in ConsSimilar to rod phototransductionDifferent opsins sensitive to different wavelengths: Red, green, blue

Color detection is determined by the relative contributions of blue, green, and red cones to retinal signal (Young-Helmholtz trichromacytheory of color vision)

Dark and Light Adaptation is the transition from photopic to scotopic vision (20-25 minutes). It’s determined by:

Dilation of pupilsRegeneration of unbleached rhodopsinAdjustment of functional circuitry

RETINAL PROCESSING

Bipolar Cells. Can be categorized in 2 classes: OFF bipolar cells (they respond to glutamate by depolarizing) and ON bipolar cells (they respond to glutamate by hyperpolarizing) . Light off or on causes depolarization

Photoreceptors release glutamate when depolarized

RETINAL PROCESSING

Ganglion Cell Receptive Fields On-Center and Off-Center cellsResponsive to differences in illumination

M-type: larger receptivefield, faster conduction of AP,more sensitive to low contrast stimuli

RETINAL PROCESSING

Color-Opponent Ganglion Cells

Two types of ganglion cells in monkey and human retinaM-type (Magno) and P-type (Parvo) – 5 and 90 % of the ganglion cell population. The rest 5 % is non-P and non-M cells

RETINAL PROCESSING

THE CENTRAL VISUAL SYSTEM

RETINOFUGAL PROJECTION

It’s the neural pathway that leaves the eye and it include: The Optic Nerve, Optic Chiasm, and Optic Tract

RETINOFUGAL PROJECTIONThe visual field is the entire region of the space that could be seen by both

eye looking straight ahead. Right and Left Visual Hemifields are defined by the space divided by the midline

nasalretinatemporal

retina

temporal retina

RETINOFUGAL PROJECTION

LGNOptic radiation

V1retinaR optic tract

V1

R LGN

R optic radiation

RETINOFUGAL PROJECTION

TransectionOptic nerve

TransectionOptic tract

TransectionOptic chiasm

THE LATERAL GENICULATE NUCLEUS

In the LGN is present the segregation of input by Eye and by Ganglion Cell Type

THE STRIATE CORTEX

Retinotopy Neighboring representation of the object are spatially kept along all the visual pathwayIn the cortex there is an overrepresentation of central visual fieldPerception is based on the brain’s interpretation of this information

THE STRIATE CORTEX

THE STRIATE CORTEX

Lamination of the Striate Cortex (I – VI)Spiny stellate cells: Spine-covered dendrites mainly in layer IVC, they receive information from LGNPyramidal cells: Spines; thick apical dendrite; mainly layers III, IVB, V, VIInhibitory neurons: Lack spines; All cortical layers; Forms local connectionsMagnocellular LGN neurons: Project to layer IVCαParvocellular LGN neurons: Project to layer IVCβKoniocellular LGN axons: Bypasses layer IV to make synapses in layers II and III

THE STRIATE CORTEX

Outputs of the Striate Cortex:Layers II, III, and IVB: Projects to other cortical areasLayer V: Projects to the superior colliculus and ponsLayer VI: Projects back to the LGN

Receptive Fields in Layer IV CLayer IVC: Monocular; center-surround receptive field (like in LGN)Layer IVCα: Insensitive to the wavelength – projection from MagnoLayer IVCβ: Center-surround color opponency - projection from Parvo

BinocularityLayers superficial to IVC: First binocular receptive fields in the visual pathway

THE STRIATE CORTEX

Ocular Dominance ColumnsInformation coming from the left and the right eye (already segregate in LGN) is kept separate in layer IV of the visual cortex

Only on layer III mixing of the information from the two eyes

THE STRIATE CORTEX

Cytochrome Oxidase Blobs Cytochrome oxidase is a mitochondrial enzyme used for cell metabolism Blobs: Cytochrome oxidase staining in cross sections of the striate cortex. Each centered on a ocular dominance stripe in layer IV

Color-sensitive, monocular, with no orientation or direction selectivity.They are specialized for the analysis of object color

The neuron observed in the space between Blobs (interblob) are binocular, with orientation or direction selectivity.

THE STRIATE CORTEX

Receptive Fields outside Layer IVCOrientation Selectivity: Neuron fires action potentials in response to bar of particular orientation

THE STRIATE CORTEX

Receptive FieldsDirection Selectivity: Neuron fires action potentials in response to moving bar of light

THE STRIATE CORTEX

Parallel Pathways: Magnocellular; Koniocellular; Parvocellular

THE STRIATE CORTEX

Cortical Module: dimension of 2x2mm. Necessary and sufficient module for the visual perception

THE EXTRASTRIATE CORTEXDorsal stream (V1, V2, V3, MT, MST, Other dorsal areas)

Analysis of visual motion and the visual control of action In Area MT (temporal lobe) most cells: Direction-selective; Respond more to the motion of objects than their shapeArea MST (parietal lobe) for navigation,directing eye movements, motion perception

Ventral stream (V1, V2, V3, V4, IT, Other ventral areas)

Perception of the visual world and the recognition of objects,Area V4 orientation and perception of color Area IT is major output of V4. Receptive fields respond to a wide variety of colors and abstract shapes. Important also for memory

THE AUDITORY AND VESTIBULAR SYSTEMS

THE NATURE OF SOUNDSound is an audible variations in air pressure, defined by:1) frequency: Number of cycles (distance between successive compressed patches)per second expressed in units called Hertz (Hz). Human Range is btw 20 Hz to 20,000 Hz2) Intensity: Difference in pressure between compressed and rarefied patches of air. It determines the loudness of the sound.

Sounds propagate at a constant speed: 343 m/sec

THE AUDITORY SYSTEM

THE MIDDLE EARSound Force (pressure) is amplified by the Ossicles, producing greater pressure at oval window (smaller surface) than tympanic membrane, in order to move more efficiently the fluid inside the cochela

The Attenuation Reflex: response where onset of loud sound causes tensor tympani and stapedius muscle contraction. It’s used to adapt ear to loud sounds, or understand speech better in noisy environment (more attenuation of low sounds)

THE INNER EAR

Perilymph: Fluid in scala vestibuli and scala tympaniEndolymph: Fluid in scala mediaEndolymph has an electric potential 80 mV more positive than perilymph (Endocochlear potential)

THE INNER EAR

Basilar Membrane is wider at apex, stiffness decreases from base to apex

THE INNER EARPressure at oval window, pushes perilymph into scala vestibuli, round window membrane bulges out. Endolymph movement bends basilar membrane near base, wave moves towards apex

THE INNER EAR

The Organ of Corti and Associated Structures. Here the mechanical energy of the sound is transformed in electrical signal by the auditory receptor cells (hair cells).Each hair cells has around 100 stereocilia.Rods of corti provide structural support. Hair cells form synapses with bipolar neurons that have their body in the spiral ganglion. Their axons form the auditory nerve

THE INNER EARTransduction by Hair CellsWhen sound arrives, basilar membrane moves. According to the movement, stereociliabends on one or the other direction: i.e. Basilar membrane upward, reticular lamina up and stereocilia bends outward

THE AUDITORY PATHWAY

Auditory nerve

Superiorolive

MGN

Auditorycortex A1

MGN

INFORMATION ABOUT THE SOUNDInformation About Sound Intensity is encoded in 2 ways:

Firing rates of neurons and number of active neuronsStimulus Frequency

Frequency sensitivity: in Basilar membrane is Highest at base, lowest at cochlea apex. This coding is kept separate along the auditory pathways (tonotopy)

Phase Locking is another way to code for frequencyConsistent firing of cell at same sound wave phase. Only for frequency below 4kHz

SOUND LOCALIZATION: HORIZONTAL PLANEInteraural time delay: Time taken for sound to reach from ear to ear

Duplex theory of sound localization:Interaural time delay: 20-2000 Hz

Interaural intensity difference: 2000-20000 Hz

Interaural intensity difference: Sound at high frequency from one side of ear

Sound waves

Sound waves

Sound waves

Sound waves

Sound shadow

Sound shadow

Sound shadow

SOUND LOCALIZATION: VERTICAL PLANE

pinnaPath 2, direct sound

Path 2, reflected sound

Path 2, direct sound

Path 2, reflected sound

Path 3, direct sound

Path 3, reflected sound

Based on reflections from the pinna

THE AUDITORY CORTEX: BA 41

Primary auditory cortex

Secondary auditory cortex

Axons leaving MGN project to auditory cortex via internal capsule in an array called Acoustic Radiation

THE VESTIBULAR SYSTEM

Importance of Vestibular SystemBalance, equilibrium, posture, head position, eye movement

The Vestibular Labyrinth

THE VESTIBULAR SYSTEM

The Otolith Organs (saccule and utricle). Detect force of gravity (linear acceleration) and tilts (change of angle) of the head.Saccule is vertically oriented and utricle horizontally oriented

Crystals of calcium carbonate

Bending of the hairstoward kinocilium: depolarization

THE VESTIBULAR SYSTEM

The Semicircular Canals. Detect rotation of the head and angular acceleration

Crista: Sheet of cells where hair cells of semicircular canals clusteredAmpulla: Bulge along canal, contains cristaCilia: Project into gelatinous cupulaKinocili oriented in same direction so all excited or inhibited together

Filled with endolymph

endolymph

Three semicircular canals on one side helps sense all possible head-rotation anglesEach Canal paired with another on opposite side of headRotation causes excitation on one side, inhibition on the other

CENTRAL VESTIBULAR PATHWAY

S1/M1 Face area

VESTIBULO-OCULAR REFLEX (VOR)

Function: Line of sight fixed on visual target

Mechanism: Senses rotations of head, commands compensatory movement of eyes in opposite direction.

Connections from semicircular canals, to vestibular nucleus, to cranial nerve nuclei excite extraocular muscles

Motion of the head

Motion of the eyes

THE SOMATO-SENSORY SYSTEM

SOMATIC SENSATIONEnables body to feel, ache, chill. Responsible for feeling of touch and painDifferent from other systems because receptors are widely distributed throughout all the body and responds to different kinds of stimuli

Types and layers of skinHairy and glabrous (hairless)Epidermis (outer) and dermis (inner)

Functions of skinProtective functionPrevents evaporation of body fluidsProvides direct contact with world

MechanoreceptorsMost somatosensory receptors are mechanoreceptors.Pacinian corpusclesRuffini's endingsMeissner's corpuscles Merkel's disksKrause end bulbs

TOUCH RECEPTORS

TOUCH RECEPTORSTwo-point discrimination varies across the body surface (Importance of fingertips over elbow). Difference in density of receptors, size of receptive fields, brain tissue devolved in processing the information

Big toesole

calf

back

lip

forearm

thumbIndex finger

PRIMARY AFFERENT AXONS

Big toe

lip

Gray matterwhite matter

Dorsal root

Dorsal root ganglion

Dorsal rootganglion cell

receptor

Spinalnerve

Dorsalroot

Primary Afferent AxonsAα, Aβ, Aδ, CC fibers mediate pain and temperatureA β mediates touch sensations

PRIMARY AFFERENT AXONS

THE SPINAL CORDDivided in spinal segments (30)- spinal nerves within 4 divisions Dermatomes (area of the skin innervate by the R and L dorsal roots of a single spinal segment) have 1-to-1 correspondence with segments

THE SPINAL CORD

Division of spinal gray matter: Dorsal horn; Intermediate zone; Ventral horn

Myelinated Aβ axons (touch-sensitive) mainly synapses in the dorsal horn with the second order sensory neurons

Dorsal Column–Medial Lemniscal PathwayTouch information ascends through dorsal column, dorsal nuclei, medial lemniscus, and ventral posterior nucleus to primary somatosensory cortex

ASCENDING PATHWAYS

The Trigeminal Touch PathwayTrigeminal nervesCranial nerves

Medial lemniscus

dorsal column nuclei

dorsal column

VPN

S1

trigeminal nucleus VPN

S1

From face

SOMATOSENSORY CORTEX

Primary is area 3bReceives dense input from VP nucleus of the thalamusLesions impair somatic sensationsElectrical stimulation evokes sensory experiences

Area 3a receive information from vestibular systemArea 1 receive information from 3b and code for textureArea 2 receive information from 3b and code for size and shape

Other areasPosterior Parietal Cortex (5,7)

SOMATOSENSORY CORTEX

Cortical Somatotopy (Homunculus)

Cortical Map PlasticityRemove digits or overstimulate – examine somatotopy before and after

Showed reorganization of cortical maps

SOMATOSENSORY CORTEX

SOMATOSENSORY CORTEX

The Posterior Parietal CortexInvolved in somatic sensation, visual stimuli, and movement planningLesion has been associated to: Agnosia, Astereoagnosia and Neglect syndrome

Pain - feeling associated to nociceptionNociception - sensory process, provides signals that trigger pain

Nociceptors: Transduction of Pain Bradykinin , Mast cell activation: Release of histamineTypes of Nociceptors: Polymodal, Mechanical, Thermal and Chemical

PAIN

Hyperalgesia: higher sensitivity to pain in tissue already damaged

Primary occurs in the damaged tissues and secondary hyperalgesia in the surroundings

Bradykinin, prostaglandins, and substance P (secondary hyperalgesia)

PAIN

Primary Afferents First pain mediated by fast axons and second pain by slower C fibers

Spinal mechanisms

brain

Dorsal root

Ventral root

PAIN ASCENDING PATHWAYS

Main differences between touch and pain pathwayNerve endings in the skinDiameter of axonsConnections in spinal cordTouch – Ascends IpsilaterallyPain – Ascends Contralaterally

Two pathways: 1) Spinothalamic Pain Pathway2) The Trigeminal Pain Pathway

Spinothalamic Pain Pathway

PAIN ASCENDING PATHWAYS

REGULATION OF PAINAfferent Regulation: gate theory of pain

Dorsalhorn

To dorsal column

To spinothalamic tract

Primary auditory cortex

Secondary auditory cortex

Descending pain control pathway. Use of serotoninStimulation of the PAG cause deep analgesia

REGULATION OF PAIN

The endogenuos opiatesOpioids and endomorphins

TEMPERATURE

Thermoreceptors“Hot” and “cold” receptors. Varying sensitivities

The Temperature PathwayIdentical to pain pathway

Cold receptors coupled to Aδand CHot receptors coupled to C

THE MOTOR SYSTEM, part I

SOMATIC MOTOR SYSTEM

Muscles and neurons that control musclesRole: Generation of coordinated movements

Parts of motor controlSpinal cord coordinated muscle contractionBrain motor programs in spinal cord

SOMATIC MOTOR SYSTEM

Types of MusclesSmooth: digestive tract, arteries, related structuresStriated: Cardiac (heart) and skeletal (bulk of body muscle mass)In each muscle there are 100 of muscle fibers innervated by a single axon from the CNS

muscle fibers

Axon from CNS

muscle

SOMATIC MOTOR SYSTEM

Somatic MusculatureAxial muscles: Trunk movementProximal muscles: Shoulder, elbow, pelvis, knee movementDistal muscles: Hands, feet, digits (fingers and toes) movement

Flexors

Extensors

SynergistAntagonist

li

Ventral hornLower motor neuron

Ventral root

Muscle fiberSpinal nerve

The Lower Motor NeuronLower motor neuron: Innervated by ventral horn of spinal cordUpper motor neuron: Supplies input to the spinal cord

THE SPINAL CORD

Alpha Motor NeuronsTwo lower motor neurons: Alpha and GammaAlpha Motor Neurons directly trigger the contraction of the muscleMotor Unit: muscle fibers + 1 alpha motor neuronMotor neuron pool: all alpha motor neuron that innervate a single muscle

Graded Control of Muscle Contraction by Alpha Motor NeuronsVarying firing rate of motor neurons (temporal summation)Recruit additional synergistic motor units. More motor units in a muscle allow for finely controlled movement by the CNS

THE SPINAL CORD

Inputs to Alpha Motor Neurons1) Information about muscle lenght2) Voluntary control of movement 3) Excitatory or inhibitory in order to generate a spinal motor program

3 1

2

THE SPINAL CORD

THE MOTOR UNITS

Types of Motor UnitsRed muscle fibers: Large number of mitochondria and enzymes, slow to contract, can sustain contractionWhite muscle fibers: Few mitochondria, anaerobic metabolism, contract and fatigue rapidlyFast motor units: Rapidly fatiguing white fibersSlow motor units: Slowly fatiguing red fibers

Normal innervation

Crossedinnervation

slow fast slow fast

slow fast Slow likeFast like

Hypertrophy: Exaggerated growth of muscle fibersAtrophy: Degeneration of muscle fibers

Muscle fiber structure Sarcolemma: external membraneMyofibrils: cylinders that contract after an APSarcoplasmic reticulum: reach of Ca2+T tubules: network that allow the AP to go through

Mitochondria Myofibrils

T tubules

Sarcoplasmic reticulum

Opening of T tubules

Sarcolemma

THE MOTOR UNITS

The Molecular Basis of Muscle ContractionZ lines: Division of myofibril into segments by disksSarcomere: Two Z lines and myofibrilThin filaments: Series of bristles. Contains actinThick filaments: Between and among thin filaments. Contains myosin

Sliding-filament model: Binding of Ca2+ to troponin causes myosin to bind to actin. Myosin heads pivot, cause filaments to slide

THE MOTOR UNITS

Muscle contractionAlpha motor neurons release AChACh produces large EPSP in muscle fibers (via nicotinic ACh receptors)EPSP evokes action potential. Action potential triggers Ca2+ release, leads to fiber contractionRelaxation, Ca2+ levels lowered by organelle reuptake

THE MOTOR UNITS

Excitation: Action potential, ACh release, EPSP, action potential in muscle fiber, depolarizationContraction: Ca2+, myosin binds actin, myosin pivots and disengages, cycle continues until Ca2+ and ATP presentRelaxation: EPSP end, resting potential, Ca2+ by ATP driven pump, myosin binding actin covered

SPINAL CONTROL

Muscle spindles: specialized structures inside the skeletal muscle. They informabout the sensory state of the muscle (proprioception)

SPINAL CONTROLThe Myotatic ReflexStretch reflex: Muscle pulled tendency to pull backFeedback loop. MonosynapticDischarge rate of sensory axons: Related to muscle lengthExample: knee-jerk reflex (stretching the quadriceps and consequent contraction)

SPINAL CONTROL

Intrafusal fibers: gamma motor neuron Extrafusal fibers: alpha motor neuron

Gamma LoopProvides additional control of alpha motor neurons and muscle contractionCircuit: Gamma motor neuron intrafusal muscle fiber Ia afferent axon alpha

SPINAL CONTROLProprioception from Golgi Tendon Organ.In series with the muscle fibers. Information about the tension applied to the muscleReverse myotatic reflex function: Regulate muscle tension within optimal range

Golgi Tendon Organ

SPINAL CONTROLSpinal InterneuronsSynaptic inputs1)Primary sensory axons2)Descending axons from brain3)Collaterals of lower motor neuron axonsSynaptic outputs: alpha motor neuron

Reciprocal inhibition: Contraction of one muscle set accompanied by relaxation of antagonist muscle Example: Myotatic reflex

Crossed-extensor reflex: Activation of extensor muscles and inhibition of flexors on opposite side

flex flex

extend extend

MOTOR PROGRAM

THE MOTOR SYSTEM, part II

THE MOTOR SYSTEM

The brain influences activity of the spinal cord in order to generate voluntary movements

Hierarchy of controls

Highest level: Strategy, the goal of the movement and best way to achieve it. Associated to neocortex and basal ganglia

Middle level: Tactics, the sequence of muscle contraction to achieve the goal. Associate to motor cortex and cerebellum

Lowest level: Execution, activation of motor neurons that generate the movement. Associated to brain stem and spinal cord

DESCENDING SPINAL TRACTS

Axons from brain descend along two major pathways Lateral Pathways: involved in voluntary of distal musculature movement under cortical controlVentromedial Pathways: involved in control of posture and locomotion, under brain stem control

THE LATERAL PATHWAYS

Base of cerebral peducle

Medullarypyramid

Corticospinaltract

Rubrospinaltract

pyramidal decussation

midbrain

Right red nucleus

THE VENTROMEDIAL PATHWAYS

Vestibular nucleus

Spinal cord

Vestibulospinaltract

Tectospinaltract

Vestibulospinal tract: information from vestibular system. Control neck and back muscles. Guide head movements

Tectospinal tract: information from retina and visual system. Guide control eye movements.

THE VENTROMEDIAL PATHWAYS

Cerebellum

Spinal cord

Reticulospinaltract

pons

Medullaryreticular formation

Pontine reticular formation

Pontine reticulospinal tract: enhance antigravity reflexs, helps maintaining a standing posture

Medullary reticulospinal tract: opposite function

THE MOTOR CORTEXArea 4 = “Primary motor cortex” or “M1”Area 6 = “Higher motor area”Lateral region Premotor area (PMA), controls distal motor unitsMedial region Supplementary motor area (SMA), controls proximal motor units

THE MOTOR CORTEXThe Contributions of Posterior Parietal and Prefrontal CortexRepresent highest levels of motor control. Help in deciding about actions and their outcome, by integrating many source of informationArea 5: Inputs from areas 3, 1, and 2Area 7: Inputs from higher-order visual cortical areas. They both project to Area 6

Instruction

Trigger

APs of PMA neuron

THE BASAL GANGLIA

Basal ganglia Project to the ventral lateral (VLo) nucleusProvides major input to area 6

Cortex Projects back to basal gangliaForms a “loop” in order to select and initiatiate willed movements

THE BASAL GANGLIAAnatomy of the Basal GangliaCaudate nucleus, putamen, globus pallidus, subthalamic nucleusSubstantia nigra: Connected to basal ganglia

THE BASAL GANGLIA

The Motor Loop: Selection and initiation of willed movementsExcitatory connection from the cortex to cells in putamenCortical activation excites putamen neurons. Inhibits globus pallidus neurons.Release cells in VLo from inhibition. Activity in VLo influences activity in SMA

THE BASAL GANGLIA

Basal Ganglia Disorders: Hypokinesia and hyperkinesia

Parkinson’s diseaseSymptoms: Bradykinesia, akinesia, rigidity and tremors of hand and jawOrganic basis: Degeneration of substantia nigra inputs to striatumDopa treatment: Facilitates production of dopamine to increase SMA activity

Huntington’s diseaseSymptoms: Hyperkinesia, dyskinesia, dementia, impaired cognitive disability, personality disorder

HemiballismusViolent, flinging movement on one side of the body

Some examples….

http://www.youtube.com/watch?v=ECkPVTZlfP8&feature=related PARKINSON

THE CEREBELLUM

Function: Sequence of muscle contractionsLesion: Ataxia, characterized by uncoordinated and inaccurate movements. Dysynergia, dysmetricAnatomy: Folia and lobules, Deep cerebellar nuclei (relay cerebellar cortical output to brain stem structures) Vermis (contributes to ventromedial pathways) Cerebellarhemispheres (contributes to lateral pathways)

THE CEREBELLUM

THE CEREBELLUMThe Motor Loop Through the Lateral CerebellumAxons from layer V pyramidal cells in the sensorimotor cortex form massive projections to ponsCorticopontocerebellar projection are 20 times larger than pyramidal tractFunction: Execution of planned, voluntary, multijoint movements