PHGY 209: Introduction to the Nervous System

Course Information

• Course name: PHGY 209
• Course title: Introduction to the Nervous System
• Instructor: David Ragsdale
• Institution: Montreal Neurological Institute
• Instructor email: [email protected]

Nervous System Overview

• The nervous system consists of approximately 100 billion neurons.
• The brain is part of the central nervous system.
• The peripheral nervous system includes afferent (sensory) and efferent (motor) fibers.
• Information processing in the brain occurs throughout the entire system.
• Neurons are electrical cells.
• Neurons communicate with each other at specialized sites called synapses.
• Neurons have diverse shapes and sizes.
• Basic neuron structure includes soma (cell body), dendrites, and axon.

Electrical Properties of Neurons

• The neuron's interior is typically -60 to -70 mV compared to the outside.
• This resting membrane potential is due to differences in ion concentrations (Na+, K+, Cl-, and A-) inside and outside the cell.
• The resting membrane potential is primarily determined by the permeability of the membrane to K+ ions.
• K+ ions leak out of the cell, creating a negative internal charge.
• Membrane permeability to Na+, and other ions is much lower.
• The sodium-potassium pump maintains ion gradients; pumping Na+ out of the cell and K+ in.

Action Potential

• Electrical impulses are action potentials.
• The signal originates at the initial segment of the axon, and moves down the axon toward the presynaptic terminal.
• These action potentials begin at the initial segment when voltage-gated sodium channels are activated and Na+ ions rush inside.
• The action potential triggers voltage-gated potassium channels to open, allowing K+ ions to flow outside of the cell.
• The peak of the action potential is determined by Na+.
• Inactivation of the Na+ channels determines the falling phase of the action potential.
• Sodium channels are targets for naturally-occurring neurotoxins.
• Sodium channels are also blocked by therapeutically important drugs (e.g. local anesthetics & antiepileptics).
• Action potential propagation is faster in axons with larger diameters.
• Myelination, consisting of Schwann cells (PNS) or oligodendrocytes (CNS), acts as an insulator accelerating the transmission of signals.
• Saltatory conduction occurs along these insulated regions.
• Nodes of Ranvier are the gaps in myelination where voltage gated sodium channels concentrate and regenerate action potentials.
• Unmyelinated axons have a slower conduction velocity.

Synaptic Transmission

• A synapse is the region of communication between two neurons.
• There are three main types of synapses: Axodendritic, Axosomatic, Axoaxonic.
• Neurotransmitters are released into the synaptic cleft, which are received by postsynaptic receptors, potentially leading to an excitatory or inhibitory postsynaptic potential.
• Excitatory postsynaptic potential (EPSP) increase the likelihood of postsynaptic firing.
• Inhibitory postsynaptic potential (IPSP) decrease the likelihood of postsynaptic firing.
• Glutamate is a main excitatory neurotransmitter in the brain.

Receptors

• Ionotropic and metabotropic receptors exist.
• AMPA receptors are ionotropic receptors and are responsible for the “fast” EPSPs.
• NMDA receptors are highly permeable to calcium.
• Metabotropic glutamate receptor (mGluRs) and GABAB receptors are involved in modulation.

Synaptic Integration

• Action potentials arise when the sum of EPSP's and IPSPs reaches or exceeds threshold.
• High frequency activity leads to synaptic plasticity, strengthening the synapse strength over time.
• Long-term potentiation (LTP) and other forms of synaptic plasticity contribute to the learning and memory mechanisms.

Neurotoxins

• Puffer fish make tetrodotoxin which blocks sodium channels.
• Phyllobates frogs secrete batrachotoxin which activates sodium channels.

Excitotoxicity

• High concentrations of glutamate can be toxic to neurons.
• Excitotoxicity results from calcium influx through NMDA receptors.
• Excitotoxicity is related to neurodegenerative diseases after a stroke, and in other cases of neuronal damage.

Inhibitory Synapses

• GABA is a primary inhibitory neurotransmitter.
• GABAA receptors trigger Cl- influx, generating IPSPs.

Neuromodulators

• Dopamine, serotonin, norepinephrine interact mostly or entirely with metabotropic receptors.
• Neuromodulators modulate the overall state of the neurons, such as mood, alertness, and attention.

Additional Information

• Multiple sclerosis is caused by myelin loss.