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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