Neural transmission

Beauty in the nervous system?

The Neuron is the Fundamental “working unit” of the nervous system

In most respects the neuron is like other cells of our body

But is different in that it can produce electrical impulses near its cell body region

That move down the axon and lead to the release of specialized neurochemicals (neurotransmitter substances) at the Synapse

Synaptic release of Neurotransmitter substances may in turn affect “postsynaptic” neurons; mostly in the dendritic regions

Historical perspective:The “Reticular Theory The nervous system was thought to be a continuous network of fibers…no individual cells

The “Golgi stain” helped us to visualize individual neurons

And led to: The Neuron Theory

There are many types of neurons:Some common types of neurons

This is our “Model Neuron”

The Neuron is also different in that the axon is typically myelinated by “glial cells”

The Shwann cell

Oligodendrocytes ( a member of the glia family)

There are many types of glial cells: all are thought to primarily provide support functions

The Neuronal communication process can be thought of as an “electro-chemical” event How is the electric signal produced? How is the Chemical event produced?

The Neuron is Like a little battery

We use an Oscilloscope to visualize electric charge

The resting Membrane potential (RMP)

Ions are responsible for the charge of a neuron Cations + Anions-

At Rest, ionic substances have different concentrations inside vs. outside the neural membrane

Passive vs Dynamic neural responses

Hyperpolarization and Depolarization Hyperpolarization- makes the RMP more negative Depolarization-makes the RMP more positive

What is special about “threshold?”

The forces of Diffusion: Concentration Gradients

The forces of Diffusion across a semi-permeable membrane

Diffusion also occurs across electrostatic gradients

The neural membrane is a semi- permeable membrane

The Neurons membrane separates the different ions

The membrane controls diffusion

By opening or closing Ion channels

If ion channels are open; diffusion across concentration and electrostatic gradients will occur

Triggering the release of RMP energy How does threshold depolarization trigger a dynamic response? –Changes membrane permeability Activating/opening ion channels -”Voltage-gated” Na+ ion channels –Open only when a critical level of depol occurs –Other ion channels then become involved

Refractory period

Once triggered, the AP is all or none, and “one-way.”

Saltatory Propagation

Myelenation and size affect speed

Multiple sclerosis (MS) is a chronic, potentially debilitating disease that affects the central nervous system, which is made up of the brain and spinal cord. Doctors and researchers think the illness is probably an autoimmune disease, which means that your immune system attacks part of your body as if it's a foreign substance.

Multiple Sclerosis is an incurable debilitating disease of the central nervous system. MS affects young to middle aged adults. Approximately 4 million worldwide have this disease. 400,000 of these people live in the United States. It can affect anyone, and can strike at anytime without warning. Once you develop this disease it will be with you for the remainder of your life, as there is no cure or known cause. Multiple Sclerosis is a degeneration of the myelin sheath surrounding nerves in the brain and spinal cord. The part of the body effected by this disease is dependant on the nerves that are damaged. Typical symptoms may include one or more of the following: loss of muscle coordination, unsteadiness, fatigue, speech difficulties, vision degradation, loss of bowel and bladder control and numbness in the extremities. Many people with MS are unable to walk without assistance, requiring wither canes, walkers or wheelchairs. A percentage are bed ridden and unable to care for themselves in any way, required around the clock care.

Resetting the RMP

Action Potential at the Terminals

The Synapse: PRESYNAPTIC and POSTSYNAPTIC processes

PRESYNAPTIC Exocytosis

Excocytosis involves microtubules

Exocytosis Voltage-dependent Ca++ channels Ca++ influx Vesicular migration Vesiclular fusion Release of NTs into synapse

NTs release into synapse

Classical NTs

NTs Terminology Post synaptic effects AcetylcholineAcetylcholine/ACH Cholinergic+/- SerotoninSerotonin/5-HTserotonergic+/- GABAGABA (gamma-amino-butyric acid) GABA-ergic- Glutamate/GluGlutamatergic+ NorpinephrineNorpinephrine /NEAdrenergic+/- DopamineDopamine /DADopaminergic+/- Enkephalin/Endorphin+/- Many other neurotransmitters are derived from precursor proteins, the so-called peptide neurotransmitters. As many as 50 different peptides have been shown to exert their effects on neural cell function.

POSTSYNAPTIC PROCESSES: NT receptors

EFFECTS OF NTs? Many factors, but all lead to: IPSPs: inhibiitory post synaptic potentials –Hyperpolarization –Decrease probability of action potential EPSPs: excitatory post synaptic potentials –Depolarization –Increase probability of action potential

Neural Integration

Neural Integration occurs mainly at axon hillock and can occur spatially or temporally

Axon Hillock

EFFECTS OF NTs? EPSP or IPSP –Depends on receptor subtype

Most General division of NT receptors- IONOTROPIC RECEPTORS

Metabotropic Receptors

Effects depend on receptor subtype

And circuits

NT-receptor interactions must stop! Enzymatic degradation

Eg…

Effects of Nerve gas exposure Neuromuscular Effects Autonomic Nervous System Effects Central Nervous System Effects Twitching Weakness Paralysis Respiratory failure Reduced Vision Small pupil size Drooling Sweating Diarrhea Nausea Abdominal pain Vomiting Headache Convulsions Coma Respiratory arrest Confusion Slurred speech Depression Respiratory depression

Reuptake

Here are the SSRIs approved by the Food and Drug Administration (FDA) specifically to treat depression, with their generic, or chemical, names followed by available brand names in parentheses: Citalopram (Celexa) Escitalopram (Lexapro) Fluoxetine (Prozac, Prozac Weekly) Paroxetine (Paxil, Paxil CR, Pexeva) Sertraline (Zoloft) These medications may also be used to treat conditions other than depression. Side effects of SSRIs All SSRIs have the same general mechanism of action and side effects. However, individual SSRIs have some different pharmacological characteristics. That means you may respond differently to certain SSRIs or have different side effects with different SSRIs.

SSRI possible side-effects Side effects of SSRIs include: Nausea Sexual dysfunction, including reduced desire or orgasm difficulties Dry mouth Headache Diarrhea Nervousness Rash Agitation Restlessness Increased sweating Weight gain Drowsiness Insomnia

Drugs may affect neural transmission in different ways