L2: Neurophysiology I

Nervous System Organization Overview

Nervous tissue is composed of two types of cells:

1. Neurons

2. Glial Cell

Neurons

they are “the” nerve cells able to transmit information

Neuron composition

• Axon = info moves away from cell body

• Dendrite = info moves towards cell body

• Cell body = integrates in- and outgoing information

How can neurons be categorized?

Number of processes:

• Multipolar, mainly in CNS (top)

• Pseudounipolar, mainly in PNS (middle)

• Bipolar, mainly sensory organs (bottom)

Function:

• Sensory (afferent): from PNS to CNS

• Motor (efferent): from CNS to muscles and glands

• Interneurons (association): relay info between neurons within the CNS

• Specialized “receptors”: transducers = convert stimuli to signal

Glial cells

non-neuronal cells; 10X more abundant than neurons (oligodendrocytes, astrocytes, ependymal cells, microglia)

Glial cells functions:

1. Provide structural support to nervous tissue

2. Participate in myelin formation (oligodendrocytes)

3. Secrete glutamate: can modulate excitatory level of neurons (astrocytes)

4. Some possess phagocytic activity (microglia)

5. Contact both blood vessels and neurons = transport of nutrients → neurons do not store glucose or Oxygen

White/Grey Matter

• Grey matter corresponds to cell bodies; integration centres

• White matter corresponds to bundles of neuron processes with the white appearance due to myelin sheaths; predominantly axons

Nerves

bundles of axons; run from or to the CNS

Cell bodies location

• Cell bodies of sensory neurons are located in clusters named ganglia (outside of the CNS)

• Cell bodies of motor nerves are located in well-defined area of the CNS (brain and spinal cord)

Myelin characteristics

• white lipid (sphingomyelin) around nerve fibres, specifically axons

• only in white matter (not all fibres)

• electrical insulations

• transmission of AP faster in myelinated fibres

How are myelin formed?

Glial cells wraps around an axon, and much of their cytoplasm is lost, leaving layers of lipid membrane around the axon

What are the interruptions between myelin sheaths

Nodes of ranvier

• every 1-2mm

• denuded axon points will allow depolarisation = transmission of action potential (AP)

How does Resting Membrane Potential (RMP) occur

• RMP results from a difference in charge across the cell membrane (between cytosol and extracellular fluid)

• Inside of membrane is negative RELATIVE to outside

• every cell of the body possesses a membrane potential

What does absolute value of RMP depend on

differs between cell type and depends on the amount of charges, ion channels and the thickness of the membrane

Average RMP in a nerve cell

–70 to –90 mV

Charges of intra- and extracellular compartments

Are electroneutral

• In the cytosol, negative charges carried by large organic molecules are attracted to the membrane by positive charges on the outside.

What maintains the RMP?

Combination of:

1. Selective permeability (passive based on diffusion)

2. Na+/K+ pump (3 Na+ out 2 K+ in)

3. Large anions trapped on the inner surface of membrane

Selective permeability (diffusion) and examples

• Passive leakage of ions through channels (concentration gradient)

• Resting membrane permeable to K+, barely permeable to Na+, Ca2+ and Cl- → positive charges accumulate outside

Ion pumps

• Concentration of ions remains relatively constant inside the cell → needs to compensate for diffusion leakage

• Na+/K+ pump: pumps 3 Na+ out and brings 2 K+ in

• Goes against concentration gradients and for Na+, against the membrane polarity (outside already positive relative to inside)

• Requires a lot of energy up to 40% of ATP availability

Excitable cells

Cells that can generate electrical impulses (Action Potentials)

How are excitable cells stimulated

Chemical, electrical or physical stimulations induce a change in membrane potential to reach a THRESHOLD provoking the opening of voltage gated ion channels

How does depolarization occur

If Na+ channels open (or Ca2+ in certain nerve endings and smooth and cardiac muscle cells), Na+ rushes inside the cell (gradient concentration) → potential less negative, then inverted (positive)

How does repolarization occur

Subsequent opening of K +channels results in an outflow of K+ returning the potential to RMP

Generation of Action Potentials in Neurons steps

1. Depolarization= an initial depolarization (stimulation) needs to reach threshold to provoke the opening of Na+ voltage gated channels

2. After about 0.5 ms, opened Na+ channels close rapidly

3. Repolarization= K+ voltage gated channels then open (delayed compared to Na+ channels) → outflow of K+

4. Hyperpolarization= K+ voltage gated channels then progressively close, outflow of K+ continues after reaching the RMP

5. Once all gated channels are closed, ions rejoin their respective compartments by diffusion and Na+/K+ pumps

6. Refractory period= Neurons cannot be re-stimulated until RMP is restored

Types of gated channels

• Voltage-gated channels

• Ligand-gated channels: binding sites for neurotransmitters

• Each channel is composed of several subunits, and has various degrees of specificity

All-or-none rule

Nerve cells follow the all-or-none rule

• When threshold is met, an AP is generated

• The amplitude of the AP is fixed for that cell

• Intensity is based on frequency of APs, not the amplitude

Conduction of action potential in unmyelinated axons

• Depolarization and repolarization processes (AP) propagate along the cell membrane

• Need for the change in potential to reach threshold on the nearby microdomain to trigger opening of gated channels

Conduction of action potential in myelinated axons

• AP occurs the same way but only at the nodes of Ranvier

• Myelin prevents ion leakage, current jumps from one node to the other = SALTATORY conduction

• Velocity increased as less membrane affected = less energy required to transport ions

Nerve velocity depends on:

Dissipation of current which is dependent on:

• thickness of myelin

• diameter of the fire (thicker=faster)

• range from 100 to 0.5 m/sec and from 2500 to 250 impulses/sec

Synpatic transmission

• Continuity of signal between a neuron and other neurons or between a neuron and target cells such as skeletal muscles (neuromuscular synapse)

• Signal sent by neurotransmitter, and neuron is triggered to reach action potential

Electric insulator

cell membrane made of phospholipids

Synaptic gap/cleft and its characteristics

a gap that exists between pre- and post- synpatic cell membranes

• rarely, direct continuity in electric impulse = gap junction (cardia and some smooth muscles)

• in vertebrates, neuronal synapses = predominantly CHEMICAL synapses

Neurotransmitters

Molecules able to transmit information from a neuron and convert the electrical signal (AP) into a chemical signal

How does a neurotransmitter work

• Released by pre-synaptic neuron into the gap

• Bind to specific receptors on post-synaptic membrane

• Elicit a response

How are neurotransmitters classified and types

• classified based on molecular size and composition

Small molecules:

• synthesized in the nerve terminals by specific enzymes

• amino acids derivatives: biogenic amines

Neuropeptides (3-40 AA):

• synthesized in the cell body

• packaged in secretory vesicles

• transported to the site of release

Steps of action in neuromuscular synapse

1. Action potential (AP)

2. At the end of the neuron, AP opens voltage gated Ca2+ channels = in-flux of Ca2+

3. Ca2+ triggers exocytosis

4. Diffusion in the cleft

5. Binding (ex. ACh) to specific receptors and Na+ gated channel opens

6. Depolarization = Ion channels open on post-synaptic membrane and reaches threshold

7. Neurotransmitter inactivated termination of signal

Postsynaptic folding purpose

is common in neuromuscular synapse (not in interneurons) which increases surface

Acetylcholine (ACh)

neuromuscular synapse transmitter

Termination of transmission for small molecules

• Picked back up by presynaptic neuron via endocytosis and recycled for next time

• Deactivated in the cleft by enzymes released by post- synaptic cell (ie Acetycholine Esterase)

Termination of transmission for neuropeptides

• After binding to its receptor, can be internalized by post-synaptic cell via endocytosis and be degraded by cellular enzymes

• Broken down by extracellular peptidase in the gap

• *Receptor can be desensitized

Integration of Multiple Synapses Between Neurons: neuro-muscular synpase

1 neuron = AP = muscle cell depolarization

Integration of Multiple Synapses Between Neurons: neuron-neuron synpase

• 1 neuron can receive impulse from multiple other neurons

• Synapses can be either excitatory or inhibitory

• 1 impulse does not always lead to a response (need to reach threshold

Excitatory synapse =

depolarization = entry of Na+

Inhibitory synapse =

hyperpolarization = entry of Cl- and/or outflow of K+

Explain these 3 graphs

A & B = excitatory neurons; C = inhibitory neurons

a) Only A activated: Excitatory postsynaptic potential (EPS) not sufficient to reach threshold as 3 impulses needed

b) A and B activated: A and B for EPS reaches threshold as meets AP

c) A,B, and C activated: C able to decrease EPS and block excitatory action of A+B