Neurotransmission ISAT 351, Spring, 2004 College of Integrated Science and Technology James Madison University.

Neurotransmission

ISAT 351, Spring, 2004

College of Integrated Science and Technology

James Madison University

Neuron Function

Neurons (nerve cells) receive, conduct, and transmit signals

Neurons carry signals from sense organs to the central nervous system (brain and spinal cord) where they are processed

From the central nervous system, neurons convey signals to muscles and glands

Neuron Structure

The cell body contains the nucleus and receives signals from other neurons on branches called dendrites or directly on the cell body

The axon conducts signals away from the cell body and divides into many branches at the nerve terminal

Neurons

Signal Signal Propagation Relay to next

Reception (electrical) cell (chemical)

Electrical & Chemical Signal Propagation

Electrical Signal Signal propagation

within neuron Branched axon

terminus amplifies signal

Terminus makes synapses with target cells

Chemical Signal Propagation between

cells Neurotransmitters Relay electrical signal

via exo- & endocytosis Targets:

Another neuron Dendrite Muscle cell

Types of Neurons

Sensory neurons receive and convert stimuli from the environment into electrical signals

Interneurons receive signals from neurons and transmits signals to neurons

Motor neurons receive signals from interneurons and stimulate muscle or glands

Structures are Similar

Neuron Signals

Electric signals transmit information within a cell from the cell body to the axon terminus by an electric impulse called an action potential

Chemical signals transmit information from sensory cells, between neurons (synapses), and to specialized cells such as muscle or glands

Nerve Signals

Neurons Form Circuits

Electrical Signal

Nerve signals are changes in the electrical potential across the neuron’s plasma membrane (membrane potential)

The action potential or nerve impulse can carry a message without signal attenuation

Action potentials actively propagate signal via voltage-gated Na+ channels

Explosion of activity propagated & amplified along membrane

Electrical Signal

Myelin sheath insulates nerve Prevents signal

attenuation Promotes signal

propagation and amplification

Multiple sclerosis involves demyelination

Electrical Signal = Action Potential

Intra- & extracellular [ion] different

[K+] high internally [Na+, Cl-] high externally

Consequences: Unequal distribution of

cations and anions Baseline membrane potential

changes when ion distribution changes

+++++++++

-

-

-

-

Propagation of Action Potential

Resting V1 V2

Baseline Membrane Action Potential Propagation :Potential -60mV -40mV Depolarization Wave

+---++++

+++---

++++---++

---+++-

Recovery

So,

Depolarizing membrane by about 20 mV triggers action potential

Voltage-Gated Channels Mediate Action Potential

•Depolarization causes channels to open and an influx of anions (Na+) causes further depolarization resulting in the action potential. •How is the membrane repolarized?

Three Conformational States

Channel inactivated until K+ ions

repolarize membrane; speeds recovery

The Action Potential

Voltage-Gated Channel

Measurement of Potential

Propagation Measurement

1 electrode inside, other outside

Stimulate & measure as a function of time

V1, V2, V3 have identical amplitudes

Shape & intensity of potential maintained

Zero attenuation as signal propagated

Consequences

All-or-none; neurons are resting or conducting Amplitude constant, so size of action potential not

important THE FREQUENCY OF ACTION POTENTIAL

FIRINGS CARRY INFORMATION RATE OF PROPAGATION FACILITATED BY

MYELIN INSULATION

Synapses Communicate Between Neurons

10-100 BILLION neurons in human brain 10-100 TRILLION synapses Human forebrain: ratio of synapses:neurons about

40,000:1 Elastic: improve connectivity by using neurons Neurons communicate via neurotransmitters:

Electrical-to-chemical-to electrical signal conversion

Electrical to Chemical Signal Conversion at Synapse

Synapses

The action potential opens voltage-gated Ca+ channels at the nerve terminal

The increase in Ca+ triggers the release of neurotransmitters into the synaptic cleft

The neurotransmitter diffuses across the synaptic cleft, binds to the target cell, and triggers an action potential

Conversion Back to Electrical Signal

Neurotransmitter Tidbits

Certain psychotic drugs (cocaine, morphine) & venoms mimic NT

Feel good with dopamine and serotonin Natural reward system appeared early in

evolution; reinforce behaviors favorable to survival

Prozac et al

Dopamine Malfunctions

• Parkinson’s disease• Insufficient dopamine due to destruction of cells that

synthesize dopamine• Motor malfunctions appear after about 70% of neurons

destroyed

• Schizophrenia hallucinations: excessive dopamine• Tourette’s syndrome: supersensitive receptors

Dopamine and Addictions

Stimulate feel good effects of dopamine using alcohol, nicotine, marijuana, and amphetamines Amphetamines stimulate secretion Cocaine keeps [dopamine] high

Dopamine may be common end-point of addictions; different mechanisms

Addicts’ feedback mechanisms impaired Consequence: dopamine deficit

Use it or lose it!

Mental activity over lifetime reinforces synaptic junctions

Learning and Memory

Thousands of nerve terminals synapse on a neuron

Combination of synapses determines if action potential is initiated

Synaptic pathways provide a mechanism to store, analyze, and recall inputs

Mult iple sclerosis (MS) is a diseasethat destroys myelin, an insulatingmaterial that coats nerve fi bers and isnecessary for normal electricalconduction in the nervous system. Thisbreakdown of the myelin, calleddemyelination, results in impairment ofthe function of the nerve.

Mult iple sclerosis (MS) is a diseasethat destroys myelin, an insulatingmaterial that coats nerve fi bers and isnecessary for normal electricalconduction in the nervous system. Thisbreakdown of the myelin, calleddemyelination, results in impairment ofthe function of the nerve.

I n MS, repeated incidents ofinfl ammation cause scarring(sclerosis) and permanentabnormal function.

I n MS, repeated incidents ofinfl ammation cause scarring(sclerosis) and permanentabnormal function.

The name is derived f rom this process- multiple (many) since it occurs in a numberof places within the nervous system andsclerosis (scars) which means the hardenedtissue that replaces damaged myelin.

The name is derived f rom this process- multiple (many) since it occurs in a numberof places within the nervous system andsclerosis (scars) which means the hardenedtissue that replaces damaged myelin.

During an MS attack, myelin becomesinfl amed, causing symptoms such as lack ofcoordination, weakness, tingling, impairedsensation, double vision or bladder problems.I f the infl ammation is severe, the myelin mayactually be damaged, however, regrowth ofmyelin may occur naturally during periods ofremission.

During an MS attack, myelin becomesinfl amed, causing symptoms such as lack ofcoordination, weakness, tingling, impairedsensation, double vision or bladder problems.I f the infl ammation is severe, the myelin mayactually be damaged, however, regrowth ofmyelin may occur naturally during periods ofremission.

Mult iple sclerosis is anautoimmune disease. Somethingcauses the body to becomeallergic to its own myelin.

Mult iple sclerosis is anautoimmune disease. Somethingcauses the body to becomeallergic to its own myelin.

MS aff ects about 250,000Americans and is about twice ascommon in women as in men.

MS aff ects about 250,000Americans and is about twice ascommon in women as in men.

There may be a genetic component--a predisposition--to susceptibility to MS. People with particular types ofhistocompatibility antigens (HLA antigens) develop MSmore of ten than those who have other HLA antigens.HLA antigens of ten associated with MS are A3, B7, andDW2.

There may be a genetic component--a predisposition--to susceptibility to MS. People with particular types ofhistocompatibility antigens (HLA antigens) develop MSmore of ten than those who have other HLA antigens.HLA antigens of ten associated with MS are A3, B7, andDW2.

Common symptoms include:

Loss of vision in one eye or double vision.

Loss of coordination and trembling of ahand.

I nstability in walking and spasticity.

Loss of bladder control.

Peculiar, spontaneous, nerve sensationssuch as a pins-and-needles feeling overpart of the body (paresthesias).

Common symptoms include:

Loss of vision in one eye or double vision.

Loss of coordination and trembling of ahand.

I nstability in walking and spasticity.

Loss of bladder control.

Peculiar, spontaneous, nerve sensationssuch as a pins-and-needles feeling overpart of the body (paresthesias).

MS is notoriously hard to diagnose.Current diagnostic tests include:

using evoked potentials (EP) to measure the rateof nerve conduction in various parts of thecentral nervous system.

Computer-assisted tomography (CT) may be usedto scan the central nervous system using an x-raytechnique which can detect areas ofdemyelination.

Magnetic resonance imaging (MRI ) may also beused to detect areas of demylenation, butwithout the use of x-rays.