MCB 244

nervous system

communication & control system

Nervous System Functions

• Collect information: Receptors detect stimuli & send sensory signals to spinal cord and brain

• Processes & evaluate information: brain & spinal cord determine response to sensory input

• Initiate response to information: brain & spinal send motor output via nerves to effectors (muscles or glands)

Central Nervous System (CNS

consists of brain & spinal cord

Peripheral Nervous System (PNS)

consists of nerves & ganglia

Sensory Nervous System

afferent nervous system; receives sensory information from receptors & transmits it to CNS

Somatic Sensory System

detects stimuli we consciously perceive

Visceral Sensory System

detects stimuli we typically do not perceive (ex: signals from heart or kidneys)

Motor Nervous System

efferent nervous system; initiates motor output & transmits it from CNS to effectors

Somatic Motor System

sends voluntary signals from CNS to skeletal muscles

Autonomic Motor System (Visceral Motor)

sends involuntary commands to heart, smooth muscle, & glands; has sympathetic & parasympathetic divisions

nerve

bundle of parallel axons in the PNS

epineurium

thick layer of dense irregular CT; encloses entire nerve

perineurium

layer of dense irregular CT; wraps fascicle (bundle of axons in a nerve)

endoneurium

delicate layer of areolar connective tissue; separates & electrically insulates each axon; wraps an individual axon

cranial nerve

nerve extending from brain

spinal nerve

nerve extending from spinal cord

sensory nerve

nerve containing sensory neurons sending signals to CNS

motor nerve

nerve containing motor neurons sending signals from CNS

mixed nerve

nerve containing both sensory & motor nerves

• most named nerves are in this category

• individual axons in these nerves transmit only one type of information

ganglion

cluster of neuron cell bodies in the PNS

neuron

structural unit of nervous system

Neuron Characteristics

• Excitability: responsiveness to a stimulus, which causes change in cell’s membrane potential

• Conductivity: ability to propagate electrical signal; voltage-gated channels along membrane open sequentially

• Secretion: release of neurotransmitter in response to conductive activity; messenger is released from the vesicle to influence target cell

• Extreme longevity: cell can live throughout person’s lifetime

• Amitotic: After fetal development, mitotic activity is lost in most neurons; cannot divide except in hippocampus & olfactory receptors in nose

cell body (soma)

part of neuron that:

• contains nucleus; plasma membrane encloses cytoplasm (perikaryon)

• Initiates some graded potentials, receives others from dendrites; conducts these potentials to axon

• Contains chromatophilic substance (Nissl bodies) made of ribosomes (free & bound)

dendrites

short, unmyelinated processes branching off cell body of neuron; receive input & transfer it to cell body

axon

long process emanating from cell body of neuron; makes contact w/ other neurons, muscles, or glands

• Attaches to cell body at axon hillock (triangular region of soma)

• Cytoplasm called axoplasm; membrane called axolemma

• Splits into branches called axon collaterals

• Ends in several telodendria (axon terminals); tips of telodendria are synaptic knobs (terminal boutons), which house synaptic vesicles containing neurotransmitter

• function to conduct action potentials & then release neurotransmitte at synaptic knobs

cytoskeleton

part of neuron composed of microfilaments, intermediate filaments, microtubules

• Intermediate filaments, termed neurofilaments, aggregate to form bundles, neurofibrils; provide tensile strength

Anterograde transport

from cell body; moves newly synthesized material toward synaptic knobs

retrograde transport

to cell body; moves used materials from axon for breakdown & recycling in soma

fast axonal transport

• Occurs at about 400 mm per day

• Involves movement along microtubules

• Powered by motor proteins that split ATP

• Anterograde or retrograde motion possible: anterograde transport of vesicles, organelles, glycoproteins, while retrograde transport of used vesicles, potentially harmful agents

slow axonal transport

• Occurs at about 0.1 to 3 mm per day

• Results from flow of axoplasm

• Substances only moved from cell body toward knob (enzymes, cytoskeletal components, new axoplasm)

structural classification

classification of neurons by number of processes coming off soma

multipolar neurons

many dendrites, one axon: most common type

bipolar neurons

one dendrite and one axon; limited number (e.g: retina of the eye)

unipolar neurons (pseudounipolar)

one process extends from cell body; splits into two processes

1. peripheral process splits into several receptive dendrites

2. central process leads to synaptic knobs in CNS

anaxonic neurons

have dendrites but no axons

functional classifcation

classification of neurons according to the direction they propagate action potentials

sensory neurons (afferent neurons)

conduct input from somatic & visceral receptors to CNS; most are unipolar (a few bipolar)

motor neurons (efferent neurons)

conduct output from CNS to somatic & visceral effectors; all are multipolar

interneurons (association neurons)

receive, process, & integrate information from many other neurons; communicate between sensory & motor neurons; located w/i CNS; make up 99% of our neurons; generally are multipolar

synapse

place where a neuron connects to another neuron or an effector; two types: chemical & electrical

electrical synapse

presynaptic & postsynaptic neurons bound together by gap junctions; fast: no synaptic delay in passing electrical signal

chemical synapse

most common type of synapse

synaptic cleft

small fluid-filled gap between two neurons

presynaptic neuron

part of synapse; axon terminal produces signal

postsynaptic neuron

part of synapse that receives signal; most commonly w/ one of its dendrites

Events of Synaptic Communication

• Neurotransmitter molecules released from vesicles of synaptic knob into cleft

• Neurotransmitter diffuses across cleft & binds to postsynaptic receptors

• Binding of neurotransmitter to receptor initiates postsynaptic potential (a graded potential)

synaptic delay

time it takes for all events of synaptic communication to occur

glial cells

non-excitable, support cells found in CNS & PNS

• approximately same number of these cells as there are neurons; account for about half the volume of nervous system

• general characteristics: capable of mitosis, protect & nourish neurons, provide physical scaffolding for nervous tissue, guide migrating neurons during development, critical for normal function at neural synapses

astrocytes

most abundant type of glial cells in CNS that have processes that end in perivascular feet

• help form blood-brain barrier by wrapping feet around brain capillaries (BBB controls which substances have access to brain)

• regulate tissue fluid composition (chemical environment around neurons) (ex: regulate potassium concentration)

• form structural support for nearby neurons

• assist in neuronal development

• alter synaptic activity (add, eliminate, influence)

• occupy space of dying neurons

ependymal cells

type of glial cells that line cavitiies in brain & spinal cord, & are part of choroid plexus, which produces cerebrospinal fluid (ESF)

microglia

small cells that wander CNS & replicate in infection, similar to the phagocytic cells of immune system; engulf infectious agents & remove debris

oligodendrocytes

large cells w/ slender extensions which wrap around axons of neurons forming myelin sheath

Glial Cells of CNS

• astrocytes

• ependymal cells

• microglia

• oligodendrocytes

Glial Cells of PNS

• satellite cells

• neurolemmocytes (Schwann cells)

satellite cells

arranged around neuronal cell bodies in a ganglion; electrically insulate and regulate the exchange of nutrients and wastes

neurolemmocytes (Schwann cells)

elongated, flat cells that ensheath PNS axons with myelin, which allows for faster AP propagation

myelination

process of wrapping an axon with myelin

myelin

Several layers of membrane of glial cells (neurolemmocytes in PNS; oligodendrocytes in CNS); high lipid content gives it glossy-whiteappearance and insulates axon

Myelination in PNS

myelination by neurolemmocytes; neurolemmocyte encircles the axon & wraps it in layers forming myelin sheath; neurolemmocyte’s cytoplasm and & nucleus are pushed to periphery forming neurilemma; a neurolemmocyte can myelinate only 1 mm of axon, so several are needed for one axon; gaps between neurolemmocytes are neurofibril nodes (nodes of Ranvier)

Myelination of CNS

Myelination by oligodendrocytes; one oligodendrocyte can myelinate 1 mm of multiple axons, each at multiple spots; no neurilemma formed; neurofibril nodes are between adjacent wrapped segments

unmyelinated axons (PNS)

axon sits in depressed portion of neurolemmocyte

unmyelinated axons (CNS)

unmyelinated axons not associated w/ oligodendrocytes

Requirements for PNS Axon Regeneration

• regeneration possible if neuron cell body is intact & if enough neurilemma remains

• successful regeneration more likely when amount of damage isn’t too extensive & when distance between site of damage & structure it innervated is shorter

Steps of PNS Axon Regeneration

1. Axon severed by trauma

2. Proximal to cut: axon seals off & swells; distal to cut: axon & sheath degenerate (Wallerian degeneration) but neurilemma survives

3. Neurilemma and endoneurium form a regeneration tube

4. Axon regenerates guided by nerve growth factors released by neurolemmocytes

5.  Axon reinnervates original effector or sensory receptor

CNS Axon Regeneration

extremely limited

• Oligodendrocytes secrete growth-inhibiting molecules; not growth factors

• Large number of axons crowd the CNS

• Regrowth obstructed by scars from astrocytes & connective tissue

pumps

Membrane proteins that maintain a concentration gradient by moving substances against their concentration gradient; require cellular energy; Neurons have Na+-K+ pumps & Ca2+ pumps in their membranes

channels

Protein pores in the membrane that allow ions to move down their concentration gradients (into or out of the cell); when open, they allow a specific type of ion to diffuse

leak channels

channels that are always open for continuous diffusion

chemically gated channels

channels that are normally closed; open when neurotransmitter binds

voltage-gated channels

channels that are normally closed, but open when membrane charge changes; V-gated Na+ channels have activation and inactivation gates

3 States of Voltage-Gated Sodium Channels

1. Resting state: activation gate closed; inactivation gate open; entry of Na+ prevented

2. Activation state: activation gate open (due to voltage change); inactivation gate open; Na+ moves through channel

3. Inactivation state: activation gate open; inactivation gate closed; entry of Na+ prevented. This state lasts a short time- channel quickly resets to resting state

modality gated channels

channels that are normally closed, but open in response to specific type of sensory

stimulus (ex: change in temperature, pressure, light)

• Found in membranes of sensory neurons that respond to changes in their environment (ex: some receptor neurons of the skin have these channels that open in response to mechanical pressure)

resting state

activation gate closed; inactivation gate open; entry of Na+ prevented

activation state

activation gate open (due to voltage change); inactivation gate open; Na+ moves through channel

inactivation state

activation gate open; inactivation gate closed; entry of Na+ revented. This state lasts a short time- the channel quickly resets to resting state

distribution of pumps & channels in entire plasma membrane of neuron

• leak channels

• Na+/K+ pumps

• maintain resting membrane potential

receptive segment

functional segment of neuron (dendrite & cell body) containing chemically-gated channels (like chemically-gated Cl- channels)

initial segment

functional segment of neuron (axon hillock) containing V-gated Na+ channels and V-gated K+ channels

Conductive segment

functional segment of neuron (axon & its branches) containing V-gated Na+ channels and V-gated K+ channels

Transmissive segment

functional segment of neuron (synaptic knobs) containing  V-gated Ca2+ channels and Ca2+ pumps

electrical energy

movement of charged particles

voltage (V)

amount of difference in electrical charge between two places, represents potential energy; measured in volts or millivolts

current (I)

movement of charged particles across barrier separating them; can be harnessed to do work

resistance (R)

opposition to movement of charged particles (i.e., the barrier); an increase in R lowers I

Ohm’s Law

Current = voltage/resistance (I = V/R), i.e., current increases w/ larger voltage & smaller resistance

RMP of Resting Neurons

-70 mV

characteristics of resting neurons

• Ions are unevenly distributed across the plasma membrane due to the actions of pumps: higher concentration of K+ in cytosol vs. interstitial fluid (IF) and higher concentrations of Na+, Cl-, Ca2+ in IF than in cytosol

• Ca2+ concentration gradient exists at synaptic knob; gated channels are closed in the functional segments of the cell

• Charge difference across the membrane is called membrane potential

  • Cytosol is relatively negative compared to IF

  • Resting membrane potential (RMP) is typically–70 mV; measured w/ microelectrodes (one inside cell; one outside) & a voltmeter

Resting Membrane Potential (RMP)

• K+ diffusion is the most important factor in setting RMP

•  K+ diffuses out of the cell due to its concentration gradient

  • limited by electrical gradient (pull of the negative RMP on positive ion)

  • If K+ were the only ion that leaked, RMP would be where the K+ concentration & electrical gradients are @ equilibrium (-90 mV)

• Since there are a few Na+ leak channels, Na+ also influences RMP

  • Na+ diffuses in due to its concentration gradient and the electrical gradient

  • This small Na+ leakage means RMP is less negative (–70 mV)

• Role of Na+/K+ pumps

  • By pushing 3 positive charges out and pushing in only 2, the pump contributes about –3 mV (of the –70 mV total)

  • More importantly, it maintains the concentration gradients for these ions

excitatory postsynaptic potential (EPSP)

Postsynaptic potential resulting in depolarization

inhibitory postsynaptic potential (IPSP)

Postsynaptic potential resulting in hyperpolarization

Graded potentials are small, short-lived changes in the RMP with the following

characteristics:

• Established in receptive segment by opening of chemically gated ion channels

• Local current changes short-lived (a few ms or less)

• Vary in degree of change & direction of change of the RMP; can be large or small & can cause a depolarization or hyperpolarization

threshold membrane potential

minimum voltage change required; typically about -55 mV

summation

(of EPSPs & IPSPs) occuring @ axon hillock; voltage changes from dendrites & soma are added; sum may or may not reach threshold membrane potential to initiate an AP

spatial summation

multiple locations on cell’s receptive regions receive neurotransmitter simultaneously & generate postsynaptic potentials

Temporal summation

a single presynaptic neuron repeatedly releases neurotransmitter & produces multiple EPSPs w/i a very short period of time (2 APs arrive @ terminal almost simultaneously)

All-or-None Law

• If threshold reached → action potential generated & propagated down axon w/o any loss in intensity

• If threshold not reached (stimulus is subthreshold) → voltage-gated channels stay

closed, no action potential

• Axon shows same intensity of response to values greater than threshold

action potential (AP)

involves depolarization & repolarization

depolarization

gain of positive charge as Na+ enters through V-gated Na+ channels

repolarization

return to negative potential as K+ exits through V-gated K+ channels