9.4 – Neuroplasticity in Adults
o Early indications
From rat brain tissue stained with radioactive tritiated thymidine –
this will only show up in newly born cells. They only had
microscopy, so skeptics assumed they could be glial cells instead
of neurons. A scientist with good reputation could not replicate the
results – they were disregarded.
Later, a new substance BrdU (Bromodeoxyurine) could label via
immunocytochemistry (vs. radioactivity) and be detected later via
antibodies the advantage of this nonradioactive compound was
that they could tag proteins only found in neurons (NeuN =
neuronal nuclei protein). Control tagged glial proteins. Showed
new neurons via this method.
• Inject BrdU > kill a few days later > expose brain tissue
Now general acceptance of new neurons, mainly in dentate gyrus
of the hippocampus and the subventricular zone.
Also shown in humans injected with BrdU (to detect cancer) –
when they died they showed neurogenesis in these areas in people
Radioactive carbon used to detect neurogenesis => about 800 new
cells / day in the dentate gyrus
o Misconception that adult neurogenesis does not occur
Discovery of growth of new neurons in songbirds directly before
new mating seasons
Via immuniohistochemical markers with selective affinity for
newly created neurons, evidence was found for neurogenesis in the
o In adult mammals, seems to be restricted to olfactory bulbs and
o The number of new neurons added to the adult hippocampus is ~2,000 /
o New olfactory bulb neurons are created from adult neural stem cells in the
subventricular zone of the lateral ventricles, before migrating to the
olfactory bulb. They then migrate via chain migration to olfactory bulb to
become new interneurons.
Neuronal precursor cells here are descendants of radial glial cells
(B cells), which subdivide asymmetrically for neurogenesis. They
o New hippocampal neurons are created in the dentate gyrus of the
Precursors from radial astrocytes, which divide asymmetrically.
They mature similarly to developing brain neurons – initially
excitatory, then become inhibitory [have a timestamp] • Hippocampal Neurogenesis and Learning and Memory
o 1. Correlational studies between neurogenesis and learning and memory
Observe learning and then check for neurogenesis in spatial tasks.
Also look at enrichment tasks – a positive correlation as a result of
physical exercise they get
o 2. Effects of learning and memory tasks on neurogenesis
Hippocampal dependent vs non hippocampal dependent tasks
• Lesioning hippocampus will produce a deficit in
hippocampal dependent behaviors
o Hippocampal lesioned rats cannot do trace
conditioning, where the CS and US are separated in
time – in normal rats the trace supports
o Vs delay conditioning, where the CS overlaps or
ends as the US begins
o 3. Effects of modulating neurogenesis on learning and memory
Low radiation doses, antimitotic drugs, genetic engineering to
Evidence not really consistent
Memantine icrases neurogenesis – NMDA antagonist
o Pattern separation – how neurogenesis can separate and pair events as
discrete temporal units.
• Hippocampal Neurogenesis and Mood regulation
o First connection suggesting this showed that hippocampal neurogenesis is
suppressed by corticosteroids, which are often elevated in individuals with
major depression and stress
o Acute and chronic treatment with antidepressants increases neurogenesis
in the dentate gyrus – in animal models of depression, which is just
essential forcing rats to do the swim talk until they learn to become
helpless [problem with the model]
But in some studies, the effects of antidepressants on neurogenesis
can be dissociated from their effects on mood.
• Adult rats living in enriched environments (variable environments, toys, running
wheels, social components) produce 60% more new hippocampal neurons vs.
Seems to depend largely on the increases in exercise that occur in
Aerobic exercise has been shown to improve cognitive function in
older adults – possible treatment for memory problems.
o These newly created neurons survive and are integrated into neural
circuits, where they begin conducting neuronal signals.
Adult generated olfactory neurons become interneurons
(connecting other neurons) Adult generated hippocampal neurons become granule cells (small
cell bodies) in the dentate gyrus
• Experience on Reorganization of Adult Cortex
o Exp. can lead to reorganization of sensory and motor cortical maps.
Tinnitus (ringing in ears) produces major reorganization of primary
Adult musicians playing string instruments w/ left hand fingering
(violin) show enlarged hand representation in right somatosensory
Anesthetizing second and fourth fingers reduces representation in
contralateral somatosensory cortex.
o Elimination of visual input to one eye of adult mice shows reduced size of
ocular dominance columns in layer IV of the primary visual cortex
These reductions occurred more quickly and were more enduring if
the mice had previously experienced visual deprivation in the same
=> Once the brain has adapted to abnormal conditions, it gains the
ability to adapt more efficiently the next time these conditions are
o Exp, on a cellular level, has been shown to increase, decrease, or modify
cortical synapses, buttons, and dendritic spines.
Causes of Brain Damage
• Tumor/neoplasm is a ma ss of cells that grouws independently of the rest of the
o ~20% are meningiomas – tumors that grow between the meninges
Encapsulated tumors – grow within their own membrane, so are
particularly easy to identify. Almost always benign – surgically
removable with little risk of further growth in the body.
o Majority are infiltrating tumors – grow diffusely through surrounding
Usually malignant tumors – difficult to remove or destroy
completely, hence, any cancerous tissue that remains after surgery
continues to grow.
o 10% are metastatic tumors – grow from infiltrating cells that are carried to
the brain via the bloodstream from another part of the body
• Cerebrovascular Disorders (Strokes)
o Strokes – sudden onset cerebrovascular disorders that cuase brain damage
via a lack of blood supply or blood leak in the brain.
Symptoms depend on the area that is affected, but commonly
amnesia, aphasia (language deficit), paralysis, coma.
Can involve a large release of excitotoxic glutamate
o Infarct – the area of dead of dying tissue produced by a stroke.
Surrounded by the penumbra – the tissue in the penumbra may
recover or die – the goal of treatment is to save this area. o Cerebral Hemorrhage – first major type of stroke
Bleeding in the brain – occurs when cerebral blood vessels rupture,
blood seeps into the surrounding neural tissue causing damage.
Can be cause by bursting aneurysms – balloonlike dilation
forming in the wall of an artery, at a point where the elasticity of
the wall is defective – can occur anywhere in the body.
• Can be congenital – present at birth.
• Can be caused by vascular poisons or infections.
• Surge in BP or contraction of blood vessels can cause the
aneurysm to burst
• Can be treated by ‘clipping’ where a clip is inserted,
causing it to coagulate and harden (not the best option b/c
risk of bursting and dying)
• Can be treated by ‘coiling’ – catheter from artery in thigh
up to brain to fill aneurysm with metal coil that causes the
blood to coagulate – can be bad if the aneurysm continues
o Cerebral Ischemia – second major type of stoke
Disruption of the blood supply to an area of the brain, caused by:
• Thrombosis – a plug, “thrombus”, composed of a blood
clot, fat, oil, air bubble, or tumor cells, forms and blocks
blood flow at the site of its formation
• Embolism – similar to thrombosis, but the plug, “embolus”,
is carried by he blood stream from the site of formation (the
larger vessel) to a smaller one, where it becomes lodged.
Essentially just a thrombus that has travelled.
• Arterioscleros – the walls of a blood vessel thicken, and
the channels narrow – this is usually the result of fat
deposits. This can eventually lead to the complete blockage
of blood vessels. Can combine with embolism and have a
Damage from a cerebral ischemia usually takes 12 days to
develop fully, and much of the damage may be associated with the
release of excess glutamate.
• Usually little evidence of brain damage directly after the
ischemic episode, but substantial loss of neurons can
usually be detected 12 days later.
• Neurons in certain areas of the hippocampus are especially
susceptible to ischemic damage (more glutamate)
• Mechanisms of damage varies by structure – astrocytes
may be implicated. Motor recovery is better than cognitive
• Blood vessel becomes blocked • Blood deprived neurons become overactive and release
• Excess glutamate binds to NMDA receptors, causing a
large influx of Sodium I and Calcium II on the postsynaptic
• The large influx eventually kills the postsynaptic neuron,
but this neuron first releases excess glutamate and spreads
the toxic cascade.
Potential use of glutamate antagonists to treat stroke victims, but
must be administered soon after the stroke as opposed to
• Closed Head Injuries
o Brain injuries produced by blows that do not penetrate the skull.
Should be treated w/ caution, esp. when confusion, sensorimotor
disturbance, or loss of consciousness ensue.
o Contusions closed head injuries that involve damage to the cerebral
circulatory system. Such damage produces internal hemorrhaging, which
can result in a hematoma, a localized collection of clotted blood in an
organ or tissue (bruising) that creates pressure on the inside of the skull.
This can be treated by drilling a hole to release the blood.
Major factor causing contusions is the harness of the skull,
occurring when the brain hits against the inside of the skull.
Blood can accumulate in the subdural space (between arachnoid
membrane and dura matter, and severely distort surrounding neural
Often occur as countercoup injuries on the opposite side of the
brain as the blow, with brain striking the skull on this opposite
o Concussion – “mild traumatic brain injury” disturbance of consciousness
following a blow to the head w/ no other evidence of structural
Substantial evidence that cognitive, motor, and neurological effects
can last many years.
Individuals who experience repeated concussions can exhibit
punch drunk syndrome, “chronic traumatic encephalopathy” which
is similar to dementia (general intellectual deterioration, memory
loss, psychosis) and cerebral scarring observed in boxers, etc. this
suggests that there is long term damage w/ concussion, even if it is
not visible after a single episode.
• Infections of the Brain
o Invasion of brain by microorganisms, resulting in inflammation known as
o Bacterial Infections
Often lead to a formation of cerebral abscesses – pockets of pus. Major cause of meningitis, inflammation of the meninges, which is
fatal in 25% of adults.
Can be eliminated by antibioitcs, but damage remains.
• Dormant for several years, then become virulent and attack
all over, including brain. The infection can incur insanity
and dementia, knows as general paresis.
o Viral Infections
Two types: those that are indiscriminant between neural and other
tissues attacked, and those that have a particular affinity for neural
• Particular affinity for the NS – fits of rage it incurs
increases chance of animals biting and spreading the virus.
• Effect on the brain almost always lethal, but there is time
for preventative vaccination before the infection has time to
spread to the brain.
Mumps and herpes attach the NS but have no special affinity for it.
o Parasitic Infections
Neurocysticerosi – tape worm in the brain – feeds of white blood
cells and immune responses (puss)
o Toxic chemicals that can enter the the GI tract, the lungs, or through the
o E.g. heavy metals like Hg (Mad hatters) or Pb (crack pots – poor drinking
out of cracked pots w/ lead inside) can accumulate in the brain and cause
permanent damage, incurring toxic psychosis.
o Drugs that are used to treat neurological disorders can have toxic effects.
Early antipsychotics caused patients to develop tardive dyskinesia,
(iatrogenic – physician induced) a motor disorder that causes
smacking/sucking of lips, puffing of cheeks, rolling/thrusting tongue,
lateral jaw movement.
o Can be endogenous – body can produce antibodies that attack NS
components, excessive glutamate release leading to strokes.
• Genetic factors
o Most neuropsychological disorders that are genetic are passed by recessive
genes – the dominant genes that disturb brain function are more readily
eliminated from the gene pool.
o Abnormal chromosome numbers
o Down syndrome (.15% of births)
Caused by an extra copy of chromosome 21 in the egg cell,
resulting in three instead of two copies in the zygote.
Characteristic disfigurement: flat nose/skull, short fingers, etc. Probability of giving birth to a child w/ downs increases greatly w/
o New preventative strategies as faulty genes are located
Splicing in healthy genes
DNAbinding proteins to block expression of the faulty gene,
• Programmed Cell Death
o Apoptosis – genetic programs for selfdestruction of cells.
Plays a role in eliminating extra brain cells during development,
and in brain damage.
All aforementioned causes of damage produce neural damage, in
part, by activating apoptotic processes.
Once through to be totally necrotic, passive cell death from injury,
but some cells that are damaged too severely will recruit enough
resources to kill themselves.
This is adaptive because in necrosis, the neurons quickly (12h)
swell and break apart, incurring an inflammatory response and
potential damage to surrounding tissue. Apoptosis occurs more
slowly (12d), starting with shrinkage of the cell body – the debris
is then packaged into vesicles, so an inflammatory response does
o Primary symptom is spontaneously recurring unprovoked (although there
are exceptions) epileptic seizure due to abnormal, excessive, or
synchronous neuronal activity in the brain but not all people w/ seizures
are considered epileptic
A one time convulsion could be caused by a toxin or high fever
o ~1% population diagnosed as epileptic at some point.
o Many seizures do not cause convulsion, but subtle changes to thought and
mood that may be perceived as normal.
o Many cases appear to be associated with faulty inhibitory synapses (e.g.
GABAergic) that may cause neurons in a particular area to fire in
synchronous bursts (rare in normal brain).
GABA tends to be excitatory in juvenile stage – adults with this
form of the receptor can be more prone to seizures
o Ictal – during the seizure; vs interictal between seizures – there can still be
EEG abnormalities here, diagnosed by “interictal spiking”
o Often identified by EEG, by high amplitude spikes – often apparent due to
an attack and also occur as individual spikes intermittently.
o Reflex Epilepsy – clear antecedent stimulus (external) that tirggers the
seizers (e.g. certain frequency lighting, reading a certain passage, orgasm
o Stress, fatigue, sleep deprevation can provoke more frequent seizures –
‘unprovoked’ in the def is kindof a misnomer o Epileptic auras , or psychological changes that some epileptics experience
before an attack.
E.g. a bad smell, feeling of familiarity, hallucination, tightness of
Can warn the patient of oncoming convulsions, and can provide
clues as to the epileptic focus.
• E.g. déjà vu focus => hippocampal focus
Technically part of the seizure, but conscious and different than
other parts of the seizure. Many people have an almost religious,
o Partial Seizures
Do not involve the entire brain. Neurons discharge in synchronous
bursts, which spreads to other areas but not nec. the whole brain.
Behavioral symptoms depend on where the focus is and the
structures that the activity spreads to – usually not associated with
a total loss of consciousness.
Simple partial seizure – symptoms are primary sensory or motor
or both (usually innocuous e.g. mouth twiching) – epileptic
discharges spread through the sensorimotor areas of the brain, and
symptoms spread systematically through the body.
• No loss of consciousness
Complex partial seizures – often restricted to the temporal lobes –
patients often engage in compulsive, repetitive, simple behaviors
(doing/undoing a button), but can also perform more complex
behaviors that appear to be normal.
• Usually have little or no recollection of the action (some
loss of consciousness is common).
• About ½ epilepsy in adults.
Secondary generalized seizure – when a partial seizure evolves
into a generalized seizure.
o Generalized seizures
Involve the entire brain. May start at a focus and spread, or may
occur almost simultaneously in the entire brain. Every electrode on
an EEG will have synchronous activity
Tonicclonic (Previously Grand mal seizure )
• Loss of consciousness, loss of equilibrium, violent tonic
extension (rigid) then pulsatile clonic (tremors)
• Tongue biting, urinary incontinence, cyanosis (turing blue
from hypoxia, ox deprivation) which can cause brain
Absence Seizure (Previously Petit mal)
• Not associated with convulsions • Associated w/ disruption of consciousness w/ cessation of
ongoing behavior, vacant look, sometimes fluttering
• Bilaterally symmetrical EEG – 3/s spike and wave
o On every electrode simultaneously – possible
thalamic focus because of connections to
everywhere else in the cortex.
• Most common in children and cease at puberty
o Epilepsy Treatments
• loss of memory, motor and cognitive speed, and these
effects usually persist after cessation (not w/ pot)
Ketogenic diet – quite effective – high fat, medium protein, no
carb – mimics the effects of fasting (reduction by ~1/2 but no side
Vagus nerve stimulation – implantation of electrode on nerve w/
pacemaker, which provides constat stimulation. Potential
activation of peripheral nervous system, decreasing arousal. Also
can be used in treatment of depression.
For severe treatment resistant epilepsy, the focus can be removed.
Corpus collosum can be severed to decrease electrical activity
between hemispheres in generalized seizures.
o Parkinson’s Disease
Movement disorder affection 12% of the elderly, more prevalent
Initial symptoms slight stiffness, tremor of the fingers
Tremor pronounced during inactivity but not during voluntary
movement, muscular rigidity, difficulty initiating movement,
slowness of movement, masklike face, pain, depression.
Shuffling gait, bradykinesia, akinesia (loss voluntary movement)
Widespread degeneration, but particularly in the substantia nigra –
midbrain nucleus that projects, via the nigrostriatal pathway, the
striatum of the basal ganglia.
Although DA is normally released by neurons of the substantia
nigra, there is little dopamine in it and in the striatum of long term
• Tyrosine > Ldopa > dopamine
Can be treated w/ Ldopa (crosses BBB more readily than DA) ,
but tolerance is developed eventually, “wearing off” – suddenly
• Diprenyl, an MAOI, can slow progression if administered
• Causes side effects, e.g. involuntary movement. • No drug that can block the progression or permanently
reduce symptom severity.
• Many use cocaine off label – powerful DA agonist
Some people believe that environmental toxins are associated
• Herbicides: Paraquat
• Fungicides: Maneb
• Pesticides: Rotanone
• Convincing animal models and epidemiological data in
All gene mutations that are associated with early onset parkinsons
have been observed to have effects on the function of the
Deep brain stimulation as a potential treatment – bilateral high
frequency stimulation to the subthalamic nucleus by a
stereotaxically implanted electrode, blocking target structure
• Alleviates symptoms within minutes, but efficacy declines
over time (doesn’t incur wering off though). Side effects
such as cognitive, speech, gait problems.
• Also a progressive motor disorder
• Stong genetic basis, rare, associated w/ severe dementia.
• Figitiness > jerky movements of entire limbs >
intellectual and motor deterioration. Death usually within
• Passed by a single dominant gene, “huntingtin”, that incurs
effects after reproductive age
• huntingtinprotein • Multiple Sclerosis
o Progressive disease attacking myelin of CNS Axons
o Eventually damage myelin until neurons become dysfunctional and
degenerate. Many areas of hard scar tissue then develop in the CNS.
o Theories of Pathogenesis
Autoimmune disorder immune modulates prevent relapsing
remittance, but underlying progression remains the same.
Primarily a neurodegenerative disease with inflammation in some
patients normal demyelination happens, but there may be a
problem with oligodendrocyte repair (problem with precursors)
• observation that myelin degredation happens from within –
immune cells would attack from the outside
o An animal model of MS can be induced by injection lab animals with
myelin and an immune stimulating preparation.
o Patients may go into remission for up to 2 years – but disease still
Visual disturbances, muscular weakness, numbness, tremor,
ataxia(loss of motor coordination), cognitive deficit, and emotional
Spasticity – muscle spasms major symptoms
o RelapsingRemitting form – symptomatic periodically. Becomes
o Primary Progressive form – virtually no immune activity when compared
o Higher concordance in monozygotic twins, females (3x), Caucasians
o Higher risk in old climate populations (vitD – could cause epigenetic
effects that express an MS gene), migrating from a high to low incidence
area at a young age can reduce chances (and opposite), and cig smokers
o No cure
• Alzheimers Disease
o Most common cause of dementia, more likely with age. 10% over 65 and
35% over 85.
Early symptoms: selective decline in memory, attention deficit,
Then confusion, irritability, anxiety, deterioration of speech
Loss of bodily functions, terminality.
o Must be officially diagnosed w/ autopsy
o Neurofibrillary tangles – threadlike tangles of protein in neural cytoplasm
Microtubules, normally stabilized by tau protein, get
hyperphosphorylated and the tubules get tangled up. o Amyloid Plaques – clumps of scar tissue composed of degeneration
neurons and betaamyloid protein
The amyloid protein misfolds, which induces clumping
o Substantial decrease in brain volume; due mainly to loss and shrinkage of
neuronal processes (synapse loss), but also due to loss of neurons
o These structures particularly prevalent in:
Memory associated structures of the medial temporal lobe:
entorhinal cortex, amygdala, hippocampus
Complex cognitive function structures: inferior temporal cortex,
posterior parietal cortex, PFCx.
NFTs and plaques heavily distributed in medial temporal and
temporal lobes (and appear here first) – could influence memory
functions that are impaired
o Big genetic component (50% siblings survining til 80s) – potentially
epigenetic mechanism. Currently no cure.
o Not clear if the primary symptom is amyloid plaques of the NF tangles.
Amyloid predominant – the three chromosomes associated w/ early
onset Alz. Influence amyloid synthesis. It also is toxic to neurons
in tissue culture.
o Many people diagnosed with mild cognitive impairment, which progresses
Low betaamyloid in CSF (can’t circulate because its coagulated)
High tau levels in CSF
Decreases in hippocampal volume (MRI)
Decreases in brain metabolism, “hypometabolism” (PET)
Some of these markers are present before a decline in function
o Theories of pathogenesis
Amyloid cascade hypothesis – plaques trigger cascade. Aluminum
potential causes misfolding of beta amyloid and sets this off. But:
• Find high plaque normal with no cognitive complains
• Amyloid does not correlate with dementia
Neurofibrillary (or tau) hypothesis – tau mutant causes
neurodegredation and tangles, but mutants for amyloid beta cause
neurodegeneration, tangles, and plaques
Vascular hypothesis (brain microbleeds)
• Many have cerebral hypoprofusion (reduced blood flow in
• Linked to vascular disease (~20%)
Animal Models of Human Neuropsychological Disease
o Rats w/ ICSS began to have seizures – Goddard noticed and planted
electrodes into the amygdala o He noticed that with a sock every day the convulsion severity would
o If stopped stimulation for 180 days, then stim reapplied the severity starts
closer to where it ended then where is started the first time – behavior
‘kindled’, relatively permanent
o Also as a model of learning and mem – same stimulation over time, but
o Needs to be enough time between applied stimulation for kindling to
occur. Longer time => less stims to kindle.
• Kindling as a model of learning and memory
o Animal can be kindled with the electrode on one side, and still has the
kindled response if after the wait period the electrode is implanted on the
other side. This happens even if the original site is destroyed.
Severity pretty much the same
Storage diffuse throughout entire brain
o Brain areas – some don’t kindle (like the cortex), most structures that are
heavily implicated in learning and memory
o Relatively permanent (like a memory)
o Transfers between brain sites
o Requires spaced vs massed stimulation
• Kindling as a Model of Epilepsy
o Electric stimulation to amygdala of rats will, over time, cause them to
develop slight tremor that will grow into generalized seizure.
o These changes remain if left unstimulated for several months, and only
arise if there is enough time separating the original stimulations
o Works w/ many species and can induced w/ subconvulsive doses of
o Can elicit epitogenesis the development of epilepsy some individuals
who experience head trauma will start having tremors that develop into
Convulsions look the same
o Does not exactly model epilepsy in that these convulsions are elicited vs
spontaneous, but applying the seizures for long enough can induce
spontaneous seizures after stimulation is ceased.
o Model for interictal behavior – can model similar emotional changes
between seizures, particularly for those suffering from complex partical
seizures (interictal changes can be worse than the seizures).
• Transgenic Models of Alzheimers in Mice
o Human defective amyloid synthesis gene injected into a newly fertilized
mouse egg then implanted into a foster mother.
o Mice show amyloid plaques with a distrubtion similar to that observed in
humans, with the highest concentration in medial temporal lobe structures.
o They also display neural loss and memory disturbances, but they do not
have NF tangles. Triple transgenic model has both. • MPTP Model of Parkinson’s
o Heroin users bought MPTP instead of MPPP (china white, a synthetic
Woke up frozen, inable to talk. One could write eventually and
they figured it out.
Similarities to parkinsons, rhythmic shaking, slow movements,
rigidity (jerking), shuffling gait, loss of facial expression
Ldopa was effective – DA necessary to translate thought of
movements inot movement
MPTP destroyed solely substantia nigra – this is the model most
o Works on primates brains in the same manner as human brains
o DA in substantia nigra (major DA source of brain) substantially reduced in
this model like the actual disease
o Some monkeys can experience a major loss in DA w/o any motor
o Led to the discover of diprenyl, a monoamine agonist that blocks the
effects of MPTP, also works in retarding the progression of the disease.
Neuroplastic Reponses to NS Damage
• Neuronal Degeneration
o Commonly modeled by cutting (autotaxonomy) of axons
o Anterograde degeneration – the degeneration of the distal segment
(between the cut and the terminals)
Occurs quickly, as the segment of the axon is separated from the
cell body, the main metabolic center
o Retrograde degeneration – degeneration of the proximal segment –
between the cut and cell body.
Progresses gradually – after 2/3 days major changes become
apparent in the cell bodies
• Can be degenerative – e.g. decrease in cell body size for
• Can be regenerative – e.g. increase in cell body size,
synthesis of more proteins to replace the degenerated
o Neuron can still die if the regenerating axon cannot
remake contact with the appropriate targt.
Transneuronal degeneration – degeneration spreading from
damaged neuron to those linked to them synaptically
• Anterograde – degeneration of neurons the dying cell
synapses onto • Retrograde – degeneration of neurons that synapse onto the
• Neuronal Regeneration
o Does not proceed successfully in mammals / higher vertebrates (does in
invertebrates) – this ability for accurate axonal growth is lost by higher
vertebrates after maturity – virtually nonexistent in CNS of adult
mammals, hit or miss in the PNS.
o In the PNS
Neurons may grow back to original locations if nerve is damaged
without severing Schwann cell sheaths
When sheaths are damaged and slightly separated, can regenerate
onto incorrect targets
Sheaths widely separated, typically no functional regeneration.
o Schwann cells allow PNS neurons to regen – they clear debris from
degradation and promote regeneration by producing neurotrophic factors
that stimulate axon growth and CAMs (cell adhesion molecules) that help
guide the growing axon
o Oligodendroglia do not clear debirs, stimulate/guide regeneration. They
actually block regeneration – they also survive for long periods,
chronically blocking regen.
o Collateral Sprouting – when an axon degenerates, and neighboring healthy
axons synapse at sites vacated by the dead neuron.
• Neuronal Reorganization.
o Kass – lesion retina and remove other – several months later primal visual
cortex neurons w/ receptive fields originally in the lesioned area now had
receptive fields in the area next to the lesion.
o Pons – cut sensory arm neurons and mapped contralateral region of
primary somatosensory cortex years later. The face area had expanded and
dominated much of this region.
o SAnes Suner Donoghue – transected motor neurons that controlled muscle
of rat whiskers – a few weeks later stimulation of the motor cortex area
responsible for this area stimulated other aresas of the face.
o Blind individuals auditory and somatosensory corticies dominate
previously visual areas – show heightened function in these other areas
• Mechanisms of Neuronal Reroganization
o Strengthening of ex