BASIC NEUROSCIENCE SERIES:INTRODUCTION AND SERIES OVERVIEW

Sindhu Ramchandren, MD, MS

AN OVERVIEW OF BASIC NEUROSCIENCE

..Or,

How the knowledge of some esoteric anatomic, cellular or signaling process may help you treat a patient

What is Neuroscience?• A scientific study of how the Nervous system (CNS and

PNS) carries out its function• What are the Nervous System’s functions?

• The Nervous System directs an individual’s ‘normal interactions’ with external stimuli

• Thus, the Nervous System includes all thoughts, perceptions, bodily actions, behaviors, and ultimately: Consciousness• Philosophical debate:

• Dualism: • Mind and Body are separate; “mind” is distinct from “brain”• Rene Descartes (1596-1650): “soul” controlled muscles via the pineal gland

by hydraulic mechanisms• Monism:

• Mind/brain is the nervous system• Rapidly gained acceptance among neuroscientists, facilitated by discovering

electricity in the 18th century (Ben Franklin, Luigi Galvani)

Evolution of the brain• The Human Brain has evolved from the inside out• Lower regions like the

brainstem are generally more ancient than higher regions, such as the frontal cortex.

• Basic survival functions like breathing are controlled in the lower brainstem

• The large prefrontal cortex in humans is a late evolution

Localization based on:•Symptoms: what the patient experiences•Signs: What the examiner observes•Helpful information:

Timing (acute, subacute, chronic)

Progression (static, step-wise regression, relapsing-remitting; progressive)

Basic Neuroscience can help..

• Interpret the clinical manifestations in physiologic terms

• Suggest treatments

What is the brain made of?

• Cells - distinct, individual cells, or networks of fused cells (syncytium, reticulum)?

• Debated by Camilo Golgi; Santiago Ramón y Cajal, etc.

• Methods: 1. Nissl and other traditional

stains2. Golgi method3. Fluorescence labelling4. Electron microscopy

• Cell types: neurons, glia, capillary endothelial cells

Building blocks• Neurons: Responsible for information

transmission throughout the Nervous system

• Cell body: contains nucleus and other biologic essentials to keep cell alive

• Dendrites: fibers that project out of the cell body, receiving info from other neurons

• Axon: transmits signals through the neuron

• Axon terminals: end of the axon; send messages to a different neuron

• Glial Cells: Support neurons by disposing waste products, stabilizing chemical environment, insulating neurons

Signaling• Communication within a

neuron is electrical• Axon- akin to the copper

wire; damage- see dimunition of size (amplitude)

• Myelin (oligodendrocytes in CNS; Schwann cells in PNS)- akin to the insulation; damage- see loss of speed (conduction velocity)

• Communication between neurons is chemical• Neurotransmitters

• Agonists: drugs that increase the activity of neurotransmitters

• Antagonists: drugs that decrease the activity of neurotransmitters

Peripheral Nervous System and disease states

A. Motor neuron: • MND

B. Nerve root:• Radiculopathy

C. Peripheral nerve:• Neuropathy

D. Neuromuscular junction:• MG/ LEMS/ Botulism

E. Muscle• Myopathy

A

B

C

D

E

Disease StatesCellular/genetic

• Anton’s syndrome (visual anasagnosia, or cortical blindness): bilateral occipital cortex lesion

• Alexia without Agraphia: (can write, but can’t read; not even what they wrote): Left occipital cortex lesion

• Gerstmann’s syndrome: Agraphia, acalculia, finger agnosia, left-right confusion: Left angular gyrus lesion

Heuristic: case-series based• Patient HM

• intractable epilepsy (perhaps due to bike accident at age 9)

• underwent surgery to remove hippocampus at age 27

• left him profoundly amnesic• Patient Phineas Gage

• Large iron rod destroyed his left frontal lobe

• Profound changes in behavior and loss of social cues

• The Man who mistook his wife for a hat (Oliver Sacks)

• Prosopagnosia, visual agnosia• The phantom within (Ramachandran and

Blakeslee)• Phantom limb pain; mirror neurons and

neural plasticity

Anatomic

• Cortical excitability: epilepsy• Cellular dropout: Basal ganglia

degenerative disorders• Neuromuscular junction blockade:

Myasthenia gravis, LEMS, Botulism• Schwann Cell mutation: Charcot-

Marie-Tooth disease (CMT, or inherited neuropathy)

How principles of Basic Neuroscience help us treat patients• Brain scans- neurons require O2 and other nutrients to function

• PET scans use a dose of radioactive glucose, which moves to the more-active areas of the brain

• fMRI detects active areas of the brain by enhancing those areas that require more O2

• Neurophysiology:• EMG/NCS: patchy slowing of conduction in several nerves can help

diagnose Chronic Inflammatory Demyelinating Polyneuropathy or its variants

• EEG: If the differential of an obtunded patient is non-convulsive status vs. metabolic encephalopathy, EEG showing Theta slowing with triphasic waves can help support metabolic/hepatic coma

• Neurotransmitters:• Allow us to manipulate disease states with appropriate uses of

agonists and antagonists.

Organization of Basic Neuroscience Series

Three “cores”1. Basic science ‘Anatomy’

• Embryology and cell type organization• Cell types by specific sites (cerebral cortex, brain stem, spinal

cord, etc.)

2. Physiology (normal)• Cellular signaling• Sensory integration (vision, balance, sensation, etc.)

3. Physiology (disease)• Specific disease states (not clinical care for them, but what went

wrong cellularly/mechanistically to result in the disease)

Last lecture of the year: “Physiology of Consciousness” By Dr. George Mashour

Online “course”

• Online Neuroscience Course Link: http://neuroscience.uth.tmc.edu/toc.htm

Example: Retinal Circuit with Lateral Inhibition Resulting in Edge Enhancement

From: http://neuroscience.uth.tmc.edu/toc.htm

Expectations• What this course will emphasize:

• Overview of basic physiology, cell types, and signaling• Overview of multiple ways the above can fail, leading to

disease states

• What it can’t do:• Clinical overview- Dr. Callaghan’s Series will cover

those, BUT we have tried to ensure that most topics are being presented by clinicians

• Pathology overview- We cannot do a whole overview of CNS/PNS pathology and also do what the Department has charged us with teaching you through this series, BUT we do have a few lectures sprinkled in

Most importantly:

• These will be available at the end of each upcoming lecture; please provide your feedback anonymously and I will review the responses

• If there are themes that become apparent in the feedback, I will make sure that subsequent lecturers are aware of what works and what doesn’t, so they can modify their talks (rather than waiting for end-of-year feedback only)

• This only works if you ATTEND the lecture and fill out the responses!

Discussion

• Beginning-of-year evaluation: expectations

• Will repeat these at end-of-year, to make sure we achieved the goals we set

• Any other thoughts or comments on ensuring a good learning experience?