CNS Cellular Organization and Communication


  • Billions of cells in CNS (10-50 times more glial cells than neurons)
    • 12-15 billion neurons in cerebral cortex
    • 1 billion in spinal cord
  • Neurons operate w/in interconnected networks
    • number of connections between neurons ranges from 1,000 to 100,000 (average 10,000)
  • Share many characteristics with other cells of bodies, but also a number of differences:
    • Have dendrites and axons
    • Communicate primarily through axonal firing, not energy exchange and intercellular transport
    • Change their behavior with experience: they learn, remember, and forget
    • Formation and regeneration: traditional view is that neurons in brain do not regenerate and unless they suffer lethal damage, live as long as person; Peripheral neurons (sensory/motor neurons) can regenerate; RECENT animal research suggests that even neurons in brain and cord may be able to regenerate to certain extent



(Classified either by morphology or function)

Morphological Classification

Defined by number of axons emanating from cell bodies

  1. Multipolar neurons (more than 2 axons)
  2. Bipolar
  3. Monopolar
  4. Interneurons: short axons or no axons that integrate neural activity w/in specific brain region

Functional Classification

  1. Motor neurons: make muscles contract
  2. Sensory neurons: respond directly to sensory info
  3. Interneurons: majority of neurons; receive input and send output to other neurons

Glial Cells

  • Glia cells (“nerve glue”) surround neurons
  • Much more numerous than neurons
  • Number of functions, including:
    • supply nutrients and oxygen to neurons
    • surround neurons to hold them in place
    • produce myelin
    • help form blood-brain barrier
    • act as housekeepers, metabolizing and removing dead neurons
    • during development, ‘radial glia’ guide migrating neurons
  • 4 types of glial cells in CNS
  1. Oligodendrocytes – form myelin of CNS (Schwann cells form myelin in PNS)
  2. Astrocytes – multiple support functions, including:
    1. provide structural support to neurons
    2. contribute to metabolism of synaptic transmission
    3. regulate ion balance
    4. support blood-brain barrier by covering blood vessels in CNS w/ “feet,” which holds the endothelial cells lining the blood vessels in place
    5. [also, astrocytes swell in rx to brain injury, which is responsible for many sxs of TBI]
  3. Ependymal cells – epithelial cells that line brain ventricles and central canal of spinal cord; assist in secretion and circulation of CSF
  4. Microglia – small cells that proliferate and act as scavengers when tissue destroyed


Neurons vary in shape and size, but have 4 common features:

Cell body (soma)

  • Functioning and survival depends on integrity, since controls and maintains neuronal structure
  • Cell bodies are gray, so areas that are dense w/ cell bodies (eg, cortex) called ‘gray matter’
  • Protein synthesis can’t take place in axon, so all axon proteins come from cell body
    • some proteins destined to be secreted as transmitters; others maintain cell
  • Some cell components:
    • Cell Membrane: surrounds entire cell; semipermeable
    • Nucleus: w/in nucleus are chromosomes (composed of DNA which contain code for controlling growth and development of cell into maturity) and a nucleolus (produces ribosomal ribonucleic acid [rRNA] which participates in formation of protein)
    • Nissl Bodies: groups of ribosomes used for protein synthesis
    • Endoplasmic reticulum (ER): system of tubes for transport of materials within cytoplasm; can have ribosomes (rough ER) or no ribosomes (smooth ER). With ribosomes, the ER is important for protein synthesis
    • Golgi Apparatus: membrane-bound structure important in packaging peptides and proteins (including neurotransmitters) into vesicles
    • Microfilaments/Neurotubules: system of transport for materials within a neuron and may be used for structural support
    • Mitochondria: most cell processes require energy, which is manufactured by mitochondria; brain cells derive all energy from glucose, which is extracted from blood as needed (brain can NOT store glucose); mitochondria takes up glucose and breaks it down for energy


  • Extensions of cell body that increase surface area and specialized to receive info from other cells
  • Number of dendrites varies by neuron, although usually thousands
  • Total possible connections among neurons in human brain approximately 10,000,000,000,000,000 -more numerous than stars in universe
  • Striking feature is ability to grow and change; one substrate for learning
    • some dendrites in elderly may be very long
    • some diseases that produce MR or dementia may be ass’d w/ reduced dendritic length or spine #
  • Shapes of dendritic ‘trees’ and spines are often among most characteristic morphologic features of neuron (eg, purkinje cells [found in cerebellar cortex] spread out in one plane and thousands of dendritic spines; pyramidal cells [found in all areas of cerebral cortex] have bodies that are pyramidal or conical


  • Originate in cell body at transition called axon hillock
  • Each cell has only one, so cell can only send one message
  • Can vary in size from a few microns to more than a meter
  • Most axons have branches called collaterals
  • At end of axon and collaterals are fine terminations called teleodendria, which end in little knobs called terminals that juncture w/ other cells
  • Can grow new teleodendria and new terminals so, along w/ dendrites, mediate learning
  • Many axons surrounded w/ myelin sheath (which is lipoprotein), giving whitish appearance
    • Speed/efficiency of action potential propagation significantly influenced by degree and integrity of myelination of axons
    • Increase of neuronal conduction conferred by saltatory conduction (from saltare, meaning “to leap”): myelin sheath interrupted every 1-2 mm by unmyelinated segment called Node of Ranvier, which permits the action potential to jump from one node to next

Terminal Synaptic Buttons

  • Near end of axon are branches w/ slightly enlarged ends called axon terminals or terminal buttons, the presynaptic portion of the synapse where electrical nerve impulses cause release of neurotransmitters
  • Synapse: site of interneuronal communication
  • Main fx of axons is to transmit electrochemical info; info travels along axon electrically, then transfers across synapses chemically; so can study brain electrically (EEG, EP, etc.) or biochemically or metabolically (PET, etc.)


Resting Membrane Potential

  • Neurons show a resting potential when inactive: slight electrical imbalance between inner and outer surfaces of membrane caused by separation of electrically charged ions
  • Ions: atoms or molecules that have acquired electrical charge by gaining or losing one or more electrons
  • Ions pass through tiny channels in axon wall to communicate
  • Four ions important: organic ions (symbolized by A-), sodium (Na+), potassium (K+), and chloride (Cl-)
  • Inside of axon is electrically negative: electrical potential difference between interior and exterior is synonymous w/ membrane potential (in range of -70 millivolts)
  • Electrical imbalance can occur b/c axon membrane is semipermeable
    • Some molecules (oxygen, water) pass thru membrane constantly
    • Other chemicals (K+, Cl-, NA+) can’t cross, so pass through gates
  • Membrane Potential is property of two opposing forces:
  1. Force of Diffusion: molecules distribute themselves equally throughout medium in which they’re dissolved
  2. Force of Electrostatic Pressure: particles w/ same kind of charge repel; different charge attract

At rest, outside of cell charged positively w/ respect to inside (out = +, in = – charge)

  • Organic anions (negatively charged)
    • Found only inside cell
    • Can’t go anywhere b/c cell membrane is impermeable to them
  • K+ is found predominantly in the intracellular fluid
    • Diffusion force pushes out
    • Electrostatic pressure pushes in
    • Two opposing forces balance
  • Cl- found predominantly in the extracellular fluid
    • Diffusion pressure pushes in
    • Electrostatic pressure pushes out
    • Two opposing forces balance
  • Na+ found predominantly in the extracellular fluid
    • Diffusion pressure pushes in
    • Electrostatic pressure does NOT prevent Na+ from entering cell
    • Thus, need sodium-potassium pump to continuously push Na+ out of cell (pump exchanges 3 sodium ions for every 2 potassium ions; pump uses up to 40% of neuron’s metabolic resources)

The Action Potential

  • To generate a nerve impulse, cell membrane must first depolarize
  • Depolarization begins when sodium channel across membrane opens and sodium ions pass through into cell, reducing voltage
  • Cause of action potential: brief drop in membrane resistance to Na+ (ions rush into cell), immediately followed by drop in membrane resistance to K+ (ions rush out of cell)
  • Depolarization occurs when membrane potential reaches about –55 mV
    • at this time, sodium gates fly open, permitting a rapid, massive, explosive flow of ions
    • in few milliseconds, see change in membrane potential from about –70 mV to about +35 mV
  • Neurons fire in All-or-None fashion
    • Subthreshold stimulation does NOT result in an action potential
    • Neuron cannot send stronger action potentials down its axon
    • Force of action potential does not depend on intensity of stimulus initiating it; in other words, strength of a signal does not matter (although neurons can be in different states of preparedness for firing)
  • Thus, only two features of the conducting signal convey information (again, intensity of stimulus doesn’t):
  1. the number of action potentials
  2. the time interval between action potentials
  • After neuron has fired, there’s an absolute refractory period that lasts one or more milliseconds when neuron incapable of firing; Absolute refractory period followed by relative refractory period, when neuron can fire but needs higher than normal levels of stimulation to do so


Communication Between Neurons

  • Transmission of info between cells dependent on chemicals including neurotransmitters, neuromodulators, and hormones
    • Neurotransmitters: released by terminal buttons of neurons and detected by receptors in membrane of another cell located short distance away
    • Neuromodulators: also released by terminal buttons, but secreted in larger amounts and diffuse for longer distances, modulating activity of many neurons in particular area (most composed of peptides)
      • Not all communication is mediated at synaptic juncture; Other parts of membrane sensitive to neuromodulators and hormones
    • Hormones: most produced in endocrine glands; cells that secrete hormones release into extracellular fluid and then distributed to rest of body thru bloodstream; only cells that have target cells for particular hormone respond to its presence
      • Two classses of hormones:
  1. Peptides – chains of amino acids linked by peptide bonds (ex include insulin and pituitary gland hormones)
  2. Steroids – very small fat-soluble molecules (ex include sex hormones and hormones secreted by adrenal cortex)
  • Synapses can occur on dendrite, cell body, or axon
  • Synapse includes: presynaptic membrane, postsynaptic membrane, and in between area called synaptic cleft
    • When action potential conducted down axon, a number of small synaptic vesicles located just inside membrane fuse w/ membrane and then break open, spilling contents into synaptic cleft
    • Then, transmitter substances attach to postsynaptic membrane at postsynaptic receptors
    • The presence of substance in cleft allows particular ions to pass through membrane, changing local membrane potential
  • Postsynaptic potentials are either brief depolarizations or hyperpolarizations of postsynaptic membrane
    • kept brief by reuptake (rapid removal of transmitter substance by terminal button) and enzymatic deactivation (enzyme destroys transmitter – occurs for acetyclcholine by way of acetylcholinesterase)
  • Nature of postsynaptic potential depends on type of ion channel opened by postsynaptic receptors at particular synapse
    • Excitatory potentials (EPSP)occur when Na+ enters cell
    • Inhibitory potentials (IPSP) produced by opening of K+ or Cl- channels
  • Temporal Summation – occurs when a burst of action potentials reaches a nerve fiber terminal; the series of impulses in one excitatory fiber can sum over time to fire a target neuron, even though each individual EPSP wouldn’t do it
  • Spatial Summation – impulses in two excitatory fibers cause two synaptic depolarizations at about the same time that together reach firing threshold; they sum over space to fire a target neuron, even though each individual EPSP wouldn’t do it
  • Rate of firing of axon of postsynaptic cell is determined by relative activity of both excitatory and inhibitory synapses on membrane of dendrites and soma – phenomenon called neural integration
  • Once receptors are activated they can produce two effects:
  1. if voltage change large enough, adjacent Na+ channels are excited and cause action potential
  2. can also initiate chemical changes within the cell, which can lead to permanent changes in number of receptors or may change other structures w/in the cell – the chemicals involved in this postsynaptic activity are called second messengers (eg, cAMP; first messenger is neurotransmitter); play role in learning


  • More than 50 different chemicals known to fx as transmitters
  • In brain, most synaptic communication is accomplished by two transmitter substances: one w/ excitatory effects (glutamate) and one with inhibitory effects (GABA)
    • in general, all other substances have modulating effects rather than info-transmitting effects; that is, release of other substances activates or inhibits entire circuits of neurons that are involved in particular brain functions
    • eg, Ach activates cortex and facilitates learning, but info that is actually learned is transmitted by neurons that secrete glutamate or GABA
  • Classification of neurotransmitters
    • Acetylcholine
  • Monoamines
    • Catecholamines (Dopamine, Norepinephrine, Epinephrine)
    • Indolamines (Serotonin)
  • Amino Acids
    • GABA, Glutamate, Glycine, Aspartate
  • Peptides (examples)
    • Opiods: enkephalins
    • Neurohypophyseals: vasopressin, oxytocin
    • Secretins: corticotropin-releasing factor
    • Insulins: insulin, insulin growth factors
    • substance P

Classic Neurotransmitters

Acetylcholine (ACh)

General Information

First transmitter discovered

Stimulates parasympathetic nervous system

Prominent role in PNS, influencing motor control; Primary transmitter found at neuromuscular juncture (all muscular movement accomplished by release of Ach)

In CNS and brain, influences alertness, attention, and memory

In Alz, have found decreased Ach fx

Mysthenia Gravis characterized by defect in Ach transmission

Location of important cell bodies and projection

In PNS: Spinal cord anterior horn → skeletal muscles

In CNS: Basal forebrain (nucleus basalis, medial septal nucleus, and nucleus of diagonal band) → cerebral cortex


formed by combination of acetyl CoA + choline; in presence of enzyme choline acetyltransferase

does not undergo reuptake; action is terminated by cholinesterase

Drug Info

Two receptor types: Nicotonic (movement) Muscarinic (both found in CNS but muscarinic predominates there)

Tacrine (Cognex): reversible anticholinestrase used to enhance cog functioning

Botulinum toxin prevents release of Ach; Black widow spider venom stimulates release; Curare blocks Ach nicotine receptors

Serotonin (5-HT, or 5-hydroxytryptamine)

General info

Behavioral effects are complex

Plays a role in regulation of mood; control of eating, sleep, and arousal; and pain

Location of important cell bodies and projection

Raphe Nuclei (in brainstem) → entire CNS

Drug info

Prozac, Paxil, Zoloft, LSD, etc. have effects on 5HT

Tricyclic antidepressants (eg, imipramine, clomipramine) block both Serotonin and NE uptake

Dopamine (DA)

General info

Generally associated w/ motor disorders and neuropsychiatric problems (schiz, ADHD, tics), as well as modulation of reward

Conditions due to defects in dopamine synthesis include PKU, Parkinson’s

Excessive dopamine produced by coke, amphetamine, L-dopa; can lead to visual hallucinations, hyperkinetic movement disorders

Location of important cell bodies and projection

Midbrain (substantia nigra, pars compacta, and ventral tegmental) → striatum, prefrontal, limbic, amygdala

3 well-known pathways:

  1. Nigrostriatal – major component of extrapyramidal motor system; decreased DA here causes rigidity, tremor, and akinesia; excess causes dyskinesia
  2. Mesolimbic – probably propagates positive sxs of psychosis; rewarding effects of certain stimuli including drugs; ventral tegmental areas (midbrain) to amygdala/limbic
  3. Mesocortical – probably propagates some neg sxs of psychosis; planning, strategy preparation; ventral tegmental to frontal cortex


Phenyalanine → tyrosine → DOPA → Dopamine (tyrosine hydroxylase rate-limiting)

Terminate process: reuptake, monoamine oxidase (MAO), etc.

Drug Info

Most antipsychotics work primarily on dopamine (eg, Haldol, Thorazine, Clozaril, Risperdal), as does L-dopa

Norepinephrine (NE) (noradrenalin)

General info

Functions complex, but probably helps regulate mood, memory, hormones, blood flow, and motor behavior

Also thought to increase vigilance; role in sexual behavior and control of appetite

Location of important cell bodies and projection

Locus Ceruleus (pons) → entire CNS

Drug Info

Tricyclic antidepressants (eg, imipramine, clomipramine) block both Serotonin and NE uptake

Epinephrine (adrenalin)

General info

Hormone produced by adrenal medulla

Also produced in brain, but minor importance compared with NE

Stimulates sympathetic division of ANS to produce “flight or fight”



  • Cell bodies in entire CNS project to entire CNS
  • Principal inhibitory transmitter substance in brain and cord
  • Enhanced activity produces sedative, anxiolytic, and anticonvulsant effects
  • Benzodiazepines (eg, diazepam/valium, xanax, ativan) thought to work by stimulating GABA
  • (markedly decreased in Huntington’s)


  • Cell bodies in entire CNS project to entire CNS
  • Principal excitatory transmitter substance in brain and cord
  • Implicated in neural plasticity, learning, and memory
  • Excessive activity associated w/ excitotoxicity
  • Four types of glutamate receptors, one being the NMDA receptor


  • Inhibitory neurotransmitter in spinal cord and lower brain
  • May play a modulatory role at interneurons in cord
  • Blocked by strychnine


  • project to entire CNS; no mechanism for reuptake once released; deactivated by enzymes
    • Enkephalin- physiological roles include pain perception, stress, respiratory regulation, temperature control, tolerance development
    • Substance P – mediator of inflammation, as well as a neurotransmitter in primary afferent fibers carrying pain signals
    • Vasopressin (aka antidiuretic hormone); acts peripherally to facilitate water reabsorption by kidneys; may play a role in memory consolidation
    • Somatostatin – modulation of heat, pain, sleep; also reduced in cortex of Alz pts
    • Angiotensin II- potent vasconstrictor activity in periphery; central actions include stimulation of pressor responses and drinking