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Brain science and Brain DiseaseClass #1

• http://osherbrainclass.blogspot.com/

Who am I?

• Nathan Urban Ph.D.

• Professor and Head, Department of Biological Sciences

– Also affiliated with the Center for the Neural Basis of Cognition

• At CMU for the last 10 years

• Working in the area of computational neuroscience/study of olfaction

Schematic of the Analytical Engine a steam-powered mechanical computer proposed by Charles Babbage c.1830(image from NY Times, 8 Nov. 2011)

Alternative implementations of computing

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Brains vs computers

CAPTCHAs –Can’t be read by computers

Addition ‐Computers are very fast and accurate

Who are you?

(Tentative) Structure of the course

• Class #1:

– Intro to class

– Description of brain structure

– Introduction to neurons, synapses and networks

• Class #2 – Neurogenesis and Depression

• Class #3 – Parkinson’s disease

• Class #4 – Alzheimer’s disease

• Class #5

Alternative topics

• ALS (Lou Gherig’s Disease)

• Autism

• Brain-machine interfaces

• Stroke and brain plasticity

• Others?

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Outline for today

• Introduction to the field of neuroscience

• Brain disorders

What is Neuroscience?

• Study of the nervous system

• Roots in physiology, psychology, medicine (neurology and psychiatry), and to some extent biology

• New field – no one called themselves neuroscientists until ~1960’s

• First undergraduate “neuroscience” department was the Psychobiology Department at UC Irvine in 1972

• Highly interdisciplinary field – people from physics, math, biology, ethology, engineering, psychology.

• Rapidly evolving – recent trends have been towards molecular neuroscience, and cognitive neuroscience. Largely these have been driven by technical advances (knockout animals, fMRI, single molecule measurements)

• Long range goals, understanding of cognitive processes, cognitive disorders

Successes of Neuroscience (as assayed by Nobel Prizes)

• Understanding the behavior of single neurons (Hodgkin and Huxley, Katz, Eccles, Neher and Sakmann, Sherrington).

• Understanding the basis of sensory perception (Mountcastle, Hubel and Wiesel).

• Understanding the biological bases of neurological and psychiatric disease (Greengard, Carlsson).

• Understanding the neurochemical basis of learning and memory (Kandel).

• Understanding genetics of olfaction and axon guidance (Axel and Buck)

• Development of optogenetic techniques for control of neuronal activity and treatment of disorders (????)

• Understanding of the biological bases of cognitive processes (????)

The Ultimate Goals of Neuroscience

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Brain anatomy

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Central vs peripheral nervous system**

• Central NS = brain and spinal cord• Peripheral NS = everything else

• cranial nerves – leave skull and connect to body

• spinal nerves – leave spinal cord and connect to body

• somatic NS (innervate skeletal muscle)

• autonomic NS• sympathetic (fight or flight)• parasympathetic (rest and

metabolism)• enteric (controls gut)

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Major Parts of the Brain** Sheets and blobs

• Cortex refers to a layered structure

– Cerebellar cortex – cerebellum not including deep cerebellar nuclei

– Cerebral cortex

• Neocortex/isocortex

– 6 layers

– Phylogenetically most recent

• Allocortex < 6 layers

– Paleocortex – anterior olfactory nucleus, piriform cortex (lizard cortex)

– Archicortex – Hippocampus and dentate gyrus

• Nuclei are unlayered collections of neurons

– Nucleus accumbus

– Nucleus of the solitary tract

Gray and white matter

• Gray matter = neurons

• White matter = axons (the wires of the brain)

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Neocortex: Sulci & Gyri

3 lbs & 2500 cm3 (~2.7 ft3)…

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Lobes of the Neocortex**

Localization of function by lesion Anatomical directions**

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Anatomical terminology** Planes of section**

A brain without stain Brains consist of two kinds of cells

• Neurons (nerve cells): Excitable cells that respond to stimuli, transmit and process information

• Glial cells (Glia): Supporting cells that help maintain electrolyte balance in brain, remove waste

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Nissl stain labels neuronal cell bodiesNeurons are the

computational units of the brain

• Neurons take thousands of inputs and convert them to a single binary output

~40 microns

010010010001000100010000010

Input current

Action potentialsor “spikes”

binary string

Human Giraffe Platypus

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Nissl Stain defines Brodman’s areas

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Brodmann’s areas

Cerebral Cortex Is Organized in Layers

• Unstained brain has very low contrast, making structure hard to see.

• Nissl staning reveals cell bodies

• Golgi staining labels entire cells

• The distinctive laminar structure of cell packing in the cortex can be seen using these staining techniques.

Synapses

• The connections between neurons are called synapses

• Each neuron may make ~ 10,000 synapses with other neurons

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Grow a brain Grow a BrainBrain size scales with body size

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Add brain areas

Icb.oxfordjournals.comIntegr. Comp. Biol. August 1, 2002 vol. 42 no. 4

Golgi Stain shows cell bodies and processes

Synapse-web.org

Spines – found on dendrites

Golgi stain is a silver-based stain that is used to label a (small) random subset of neurons

Single neuron

Golgi stained mouse brain Golgi stain

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Cajal and GolgiCamillo Golgi

Developed staining technique that allowed complete structure of neurons to be visualized. Believed that neurons were physically connected, forming a “reticulum”.

Santiago Ramon y Cajal

Believed that neurons were individual cells connected to each other by chemical transmission. The term “synapse” was later coined by Sherrington.

Cajal and Golgi shared the Nobel Prize in 1906 – “in recognition of their work on the structure of the nervous system"

Debate was not completely resolved until 1950s with advent of electron microscopy

Nobelprize.org

Make a new neuron typeAllman’s von Economo neuron

Fig. 1. Photomicrographs of soma and proximal dendrites of (a) apyramidal and (b) the VENs stained with the Golgi method. Photomicrogaphsare montages taken of several planes and/or fields of view.Scale bar applies to both images.http://www.allmanlab.caltech.edu/PDFs/WatsonGolgi2006.pdf

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