HMB200 Term Test 2

Neural Mechanisms of Action \= motor action is guided by information from all over the NS

1) visual info required to locate target →

2) frontal-lobe motor areas plan the reach and command movement →

3) spinal cord carries info to hand →

4) motor neurons carry message to muscles of the hand and forearm →

5) sensory receptors on fingers send messages to sensory cortex saying that the cup has been grasped →

6) spinal cord carries sensory info to brain →

7) basal ganglia judge grasp forces, and cerebellum corrects movement errors →

8) sensory cortex receives message that the cup has been grasped

Role of the Frontal cortex \=

\-different regions may play different roles

\*where it starts

\- Prefrontal cortex = planning

\-Premotor cortex = sequence organization

\-Primary motor cortex (M1) = movement production (contains homunculus)

Motor Cortex vs Somatosensory cortex

motor cortex = frontal lobe, just anterior to brain's central fissure

\-Sensory cortex = posterior to the central fissure + extends into the parietal lobe

\*representation proportional to utility rather than size

Code of the motor cortex

Activity is evident before movement begins (not just firing before movement begins)

\-Firing of the motor neurons before a task is proportional to the muscle force required for that task (rate encoding)

Mental rehearsal/visualization

Imaging movement produces a similar pattern of brain activity to planning movement (but less strong, 30%) = similar circuit to what is used in the action

\-Often used in training athletes in technically demanding sports, may help improve performance

\*mentally rehearse it

It was originally thought that there was direct mapping of the motor homunculus neurons to muscle fibers in the periphery. HOWEVER, recent evidence suggests this is likely not the case. What is more likely \=

the regions of the motor homunculus represent categories of movement (a movement repertoire) → different parts for different actions

M1: movement repertoire Theory

Certain areas when stimulated are associated with certain movements

Sequencing motor actions

Humans can learn to execute complicated series of motor actions (such as dancing), each step in the series is reliant on the previous step

\-Lesion to the premotor cortex in animals impairs the ability to coordinate motor sequences (lasting deficits = harder to impossible to sequence the movement)

Mirror Neurons

In monkeys, neurons exist which respond to both seeing action and performing action (mirror neurons)

\*response when witnessing actions of others

\-These neurons are found in several areas, including the premotor cortex and inferior parietal lobule (learning action sequences and performing action sequences)

\*brain resonates with movement → role in learning motor activity and understanding people

\-These cells were originally thought to play a vital role in motor skills, speech and social interaction

broken mirror theory

(not a lot of support) Malfunction in these systems was thought to be a contributing factor to autism (disorder that involves difficulties in replicating/understanding actions)

Issues with mirror neurons

These intriguing theories have not been strongly supported by data

\-Mirror neurons are hard to identify in humans, studies of them becoming less frequent

\*studies are in animals, haven't been seen in humans \*difficult to find in humans b/c invasive

Commands for voluntary motor action begin with the activation of

upper motor neurons (Betz cells) → axons pass through the thalamus vis the internal capsule (very long)

\- Motor neuron axons form motor tracts, evident in the cerebral peduncles (midbrain) and pyramid (medulla - contains the descending motor tracts)

\-Tracts synapse with lower motor neurons in the spinal cord, which in turn affect muscle activity (paramital effects = the tracts)

\*damage = impairs ability to sequence actions (one example)

M1 plasticity w/ injury

Cortical representation is plastic and changes with injury as well as experience

\-If you lesion only a part of the M1 associates with the hand + digits, the whole areas shrinks (in animals)

\-Shrinkage may be mitigated (reduced) by rehabilitation

Damage to the FC cortex

Traumatic head injury, Tumor, Neurological diseases (eg. amyotrophic lateral sclerosis), Stroke (most common)

Stroke

\-Condition in which poor blood flow results in cell death and loss of brain function

\-Not all parts are equally vulnerable (might have neuronal death

\-Arises due to issues in the cerebrovascular system that supplies the brain with blood

\-Serious consequences for neurons, which depend upon blood for oxygen and glucose

\*the hippocampus is especially vulnerable to interruptions in blood supply,

Damage to motor neurons in frontal cortex can profoundly impair movement

ischemic stroke

Clot stops the blood supply to an area of the brain

hemorrhagic stroke

hemorrhage /blood leaks into brain tissue

Main arteries in the brain \=

\-Anterior cerebral artery (supplies to the dorsal-medial/frontal and parietal)

\-Middle cerebral artery (supplies to frontal, parietal, occipital)

\-Posterior cerebral artery (supplies to the occipital and some temporal)

CIMT \= constraint-induced motor therapy

Developed by Edward Taub;

\-Involves forced use of affected limb by suppressing the unaffected limb;

\-Therapy is based on the principle that loss of sensory function (afferent input to spinal cord/brain) does not always result in complete loss of motor function (efferent) *ie. Recover motor function after a stroke*

\-certain neurons may die for the movement in certain movements (ie. a hand) → but the forced use of the impaired hand may recover a limited amount of function in it

\-Restraints = braces, mitts, casting

CIMT and neuroplasticity

In individuals who regain motor function, there is increased grey matter

\-Recover is imperfect → but even a little bit is valuable

\-The grey matter changes in ones with the therapy are absent in those that dont get it

\-There is more grey matter → due to rewiring and increase in connections + more elaborate processing\*not interpreted as more neurons (rarely the case)

CIMT in practice

Involves shaping (the reinforcement of successive approximations of the movement)

\-Encourages parts of the action a bit at a time; Time-intensive (90% of waking hours) and labor-intensive (requires supervision)

\-Early goal is cortical stimulation rather than task completion (which is very difficult)

\-Focus on day-to-day tasks (writing, eating, doing the dishes, etc0

Cranial and Spinal Nerves

12 cranial nerves and 31 spinal (peripheral) nerves; Almost all, but I, II, VIII have a motor component

Laterality of cranial nerves

Most cranial nerves do not decussate before entering the brainstem (ie. CNS)

\-Their associated pathways inside the CNS also do not generally decussate Lack of decussation means that most cranial nerves mediate function on the ipsilateral side of the body: Damage to most cranial nerves generally leads to impairment on the same side of the body

Ex) Bell's Palsy

Facial Nerve (VII)

\-Responsible for motor function within the face as well as sensory functions (eg. taste)

\-Malfunctions in the facial nerve can cause motor impairments

\-The facial nerve travels through a "tight tunnel" (bone)

\-Inflammation of the nerve can lead to it being compressed against the tunnel

\-Compression impairs motor function in the face

Treatment of Bell's Palsy:

Most patients recover on their own

\-In severe cases, corticosteroids (to reduce inflammation) might be recommended

\-Value of antiviral drugs is unclear

\-Surgery (to improve passage of the nerve) is possible but comes with high risks

\-Physical therapy or plastic surgery (rarely) might also be considered

In the spinal cord ...

31 segments + nerve pairs: Cervical (C1-C8), Thoracic (T1-T12), Lumbar (L1-L5), Sacral (S1-S5), Coccygeal

Motor impairment with SC injury

\-C4 injury (cervical) = Tetraplegia (head down)

\-C6 injury (cervical) = Tetraplegia (neck down)

\-T6 injury (thoracic) = Paraplegia (chest down)

\-L1 injury (lumbar) = Paraplegia (hips down)

Sensory pathways are afferent, Includes...

the dorsal column medial lemniscus system (Gracile fasciculus, Cuneate fasciculus) + Includes the spinocerebellar tracts (Posterior, Anterior) + Includes the anterolateral system (Lateral spinothalamic tract, Anterior spinothalamic tract) + Includes the spino-olivary fibers

Motor pathways are efferent, Includes...

the pyramidal tracts (clustering in bottom of brainstem in shape of pyramid) \= Lateral corticospinal, Anterior corticospinal + Includes the extrapyramidal tracts (Rubrospinal, Reticulospinal, Olivospinal, Vestibulospinal)

Sensory pathways are in the... vs Motor pathways are in the ...

sensory - dorsal (posterior) region

motor - ventral (anterior) region

Dorsolateral Column \=

lateral corticospinal pathway and the rubrospinal pathway (contacts Reds Nucleus)

Ventromedial Column \=

\-Anterior corticospinal pathway, Anteromedial Pathway System: vestibulospinal (connected vestibular nucleus for CN8) = balance and head turning (automatic system)

\-Reticulospinal (connected with reticular formation) = locomotion and posture

\-Tectospinal - tectum of midbrain - pathway (connected with superior colliculus) = orientation to stimuli - visual, head/neck/eye movement

how are tracts of the spinal cord named

*tracts are typically named from their starting location and terminal destination ex) corticospinal \= cortex to SC

Corticospinal tract: Two division

Lateral \= carries commands for movement of limbs and digits (distal muscles) + Anterior \= carries commands for movement of body's midline (proximal muscles, eg. trunk)

Decussation of the CS tracts

The lateral corticospinal tract decussates at the medulla, before the SC (90% of fibers)

\-The anterior decussates at the level of the lower motor neurons in the SC (10% of fibers)

Rubrospinal tract

\-An extrapyramidal (outside pyramidal) tract

\-Involves Red Nucleus at the level of the midbrain

\-Important for large muscle movement and coordinating fine movements (in animals)

\-May be more functionally significant in other animals

Problem with SC lesions

Neurons are still there, there just isn't a connection

\-Could cut out the middle man ⇒ deliver it themselves

\-No sensory info coming in, no motor instructions out; If we could measure the signals ....We could perhaps transfer them directly to the muscles or another apparatus (eg. machine)

\-To bypass the injury of the SC \*measure the cell activity properly and connect to a machine for tht code

Many researchers are experimenting with implants to measure neural activity (eg. Neuralink)

\-Robot-guided movement

\-Once have the correct signal, can direct it to a machine that can complete the movement

\-The individual can learn to control their movements better through the machine (feedback is vital)

\-Much research into this possibility

Basal ganglia

Network of structures involved in coordinating movement

\-judges the grasp force

\-Caudate + putamen (together = striatum)

\-Globus pallidus (internal and external) = GPe/GP

\-Subthalamic nucleus (STN)

\-Substantia nigra = provides vital input to the circuit

what does the cerebellum do for movement ...

correct movement errors

The direct pathway through the BG is thought to play an important role in

initiating movements

The indirect pathway is through the BG is thought to play a role in

inhibiting unwanted movements

For substantia nigra \=

Inhibitory actions of the DA are mediated by D2 receptors (left, indirect), whereas excitatory actions are mediated by D1 receptors (right, direct)

Pathogenesis of Parkinson's Disease (PD)

If live long enough, losing neurons all the time (so could be likely for anyone)

\-With the loss of DA-projecting neurons, the motor system is profoundly affected

\-Loss of DA-projecting neurons (>60%) is the defining feature of PD

What is PD?

Progressive disorder of the NS that affects movement

\-Develops gradually, advancing over time

\-Though primarily considered a motor disorder, involves non motor symptoms

Motor symptoms of PD

\-Resting tremor

\-Cogwheel rigidity

\-Stiffness and jerky motions

\-Decreased range of motion

\-Bradykinesia/akinesi

\-Slow to start and finish movements

\-Less spontaneous movemen

\-Difficulty w/ repeated movements

\-Decreased facial expressivity

\-Short, shuffling steps

\-Postural instability

\-Loss of balance when standing or when pressure is applied

Non-motor symptoms of PD

\-May occur before motor symptoms (predictor of later diagnosis)

\-Examples: loss of smell, constipation, sleep disorders (REM), mood disorders, orthostatic hypotension, cognitive deficits (dementia)

\-Pathological gambling occurs more frequently (3.4-6.1%) than in the general population (0.25-2%) (3x the risk)

\-Other impulse control disorders are also more common, including binge eating, compulsive shopping, "hypersexuality"

\-Risk for impulse control disorders may be linked to medications for the disorder, though this is still CONTROVERSIAL

Etiology of PD

Environmental factors, Pesticide exposure, Agricultural occupation, Prior head injury, Rural living, Beta-blocker use, Well-water drinking, Genetic factors (family history): Alpha-synuclein gene (x1.5 risk), Approx 18 genes linked to PD, Heritability \= 0.40 (out of 1)

Increasing DA in PD

We cannot administer DA directly (b/c won't cross the blood-brain barrier) so need different solution: L-DOPA = immediate precursor for DA, can cross the blood barrier

\-If administer L-DOPA (levodopa; in drug form), it will be converted to DA inside the brain, correcting the DA deficiency

The metabolism of the DA

ie) monoamine oxidase B (MAOB) inhibitors = delay the breakdown of DA by MAO-: Used as monotherapy or in conjunction with L-DOPA, can reduce the dosage of L-DOPA by 15%,

ie) Catechol O-Methyltransferase (COMPT) inhibitors = delay the breakdown of DA by COMT: Mainly used in combo with L-DOPA, increasing the half life of L-DOPA; Delays the "wearing off" effect of L-DOPA and other motor complications such as dyskinesia

*but issues with L-DOPA treatments:

L-DOPA non-selectively increases DA levels in the entire brain, not just the substantia nigra (so other systems of cognition are affected),

\-Increased DA elicited by L-DOPA is not as precise as endogenous DA neurotransmission → sometimes the effects are too strong or too weak (some regions given too much DA)

\-L-DOPA has unpleasant side effects (nausea, dyskinesia, psychosis, delusion → schizophrenia)

Possible motor pathways changes instead of L-DOPA treatments

\-Change the activity in the STN and GPi/GPe with implanted electrodes

\-Deep Brain Stimulation (DBS) in PD: Electrodes can be planted into the subthalamic nucleus (more effective, preferred) or the globus pallidus internus to modulate the activity of these structures

\-Option for patients who are unresponsive to medication or suffer severe side effects \*DOES NOT cure PD, patients still need with medication (though use may decrease),

\-Mechanisms are not well understood = many stimulation parameters have been tried thus far

\-Though generally safe, DBS is invasive and can have complications (ie. if gets moved = more damage)

Cerebellum in Movement

Role in posture, balance, coordination and adapting movements

\-Contains a topographic representation of the body

\-ex) throwing darts = throws are consistent, with prisms on they change and then adapt to be more consistent, and when remove, have to adapt again to consistent, but if damage = can't correct the throws with or without the prisms, very inconsistent

Key Concept \= development refers to a

change in a specific property over time (eg. brain size), a developmental trajectory refers to the normal rate of change in a group (eg. brain size in humans), abnormal trajectories are often associated with impairments

Steps OF PRENATAL DEVELOPMENT :

1. Induction of the neural plate
2. Neuronal proliferation
3. Neuronal migration + aggregation
4. Axonal growth + synapse formation
5. Neuronal death + synapse elimination

0 - The Beginning

Begins when the sperm fertilizes the egg, making the zygote

\-The blastocyst implants around 7-10 days and continues to develop

1 - Neural Plate

Approx 18 days after conception, embryo has 3 layers: Ectoderm (outside), Mesoderm (middle), Endoderm (inside)

\-Neural plate is on the ectoderm

\-Formation of the neural plate is induced by chemicals from the mesadorm

\-Neural plate will become the NS

In the neural plate

Cells are stem cells = Important properties: Nearly unlimited capacity for self-renewal (in artificial condition

ie. culture, Pluripotent (can develop into many cell types)

\-Division produces a new stem cell + another cell (of some other type)

Terminology

Totipotent \> pluripotent \> multipotent \> unipotent

Over time, the neural plate ...

Folds to form neural groove

\-Sides of neural groove fuse to form neural tube (24 days)

\-Very early in development

\-Where circulation start: Tube center will become the ventricular system + spinal canal (for the CSF)

\-Growths on the anterior of the tube (approx 40 days) later become midbrain, hindbrain + forebrain, Early aspects forming

2 - Neuronal Proliferation

Progenitor cells divide thickness of tube increases with more cells

\-Most division occurs in the ventricular zone (tube inferior)

\-Proliferation affected chemical signals from the dorsal surface (roof plate) + ventral surface (floor plate) of tube

\-Some cells along the ventricular zone may retain this capacity

\-Can see this proliferation (so very small extent) in the adult brain

\*For the adult brain → most are generated during this time

3 - Migration

\*see layers = layers contain the same type

\-Movement of cells to their target locations

\-Inside-out process (outside layers migrate last) → inner filled first and then outer

\-At this stage, cells lack processes (no dendrite/axons)

Migration may be tangential or radial - moving outwards into diff layers (cell type)

\*Not random, Mediated by diff mechanisms

Methods of migration

Somal translocation (works for both): Extension is directed by "attractive" and "repellent" chemical cues

vs

Glia-mediated migration (radial only): Migration guided by networks of radial glial cells, Moves along the rope to get to their destination

Aggregation

Neurons align with other neurons in the same area, Cell adhesion molecules (CAMs) vital here,

\-CAMs are present on surface of cells, CAMS recognize other cells and adhere to them, Gap junctions prevalent during this period (especially in glial)

\*an electrical connection

4 - Axonal growth

Axons grow outward to their targets

\-Very precise process

\-At the end of each axon is a growth cone

\-Each cone has filopodia (finger-like extensions) = "search" extend + retract

\-Reach outward to connect with chemical signals

\-Growth is guided by chemical processes,

\-The growth cone \*elements of the neuronal cytoskeleton

Sperry's Experiments

\*specific mapping process - configuration of the areas to specific regions

\-When an insect is dangled in front of a normal frog, the frog strikes at it accurately with its tongue,

\-With eye rotation: When the eye is rotated 180˚ without cutting the optic nerve, the frog misdirects its strikes by 180˚

\*still projects, but no longer an easy alignment

\*region are no longer aligned → path is different

With Optic Nerve cut, eye rotation = When the optic nerve is cut and the eye is rotated by 180˚, at first the frog is blind; but once the optic nerve has regenerated, the frog misdirects its strikes by 180˚

This is because the axons of the optic nerve, although rotated, grow back to their original synaptic sites

\*grows back to original target despite not being aligned \*not just spatial memory

Axonal growth

Small group of pioneer axons moves first

\-Growth cones responds to various chemical signals

\-Attractants + repellants

\-Released by neurons + other cells in the matrix

\-Other axons will follow the pioneer axons later, forming axonal bundles (eg. tracts)

\-Fasciculation (when the growth of one pioneer axon, the others growth on top of it)

1. First of Axonal Deviation theory \= chemoaffinity hypothesis

Each neuron releases one factor to which it is sensitive, and that will guide the growth,

\-The axon (pre-synaptic) is guided towards its target cell (post-synaptic) because that cell releases special chemicals,

\-Cell A releases chemical

\-Axon B is sensitive to chemical X but axon C it not,

\-Axon B grows toward cell A, but axon C does not,

\-However, evidence suggests that this signalling is not simply point-to-point (eg. A to B) but more complex

Lesion studies for the first theory

In these studies, the retina or tectum were lesioned

\*the conc of the chemicals present is also important

\-If an area loses its normal axonal input, it will receive input from other axons instead (1),

\-If axons have "lost" their normal target, they will project ot another target instead \*the remaining cells take up all the rest of the space in the target

\*grow towards targets they normally wouldn't b/c they still have chemicals

2. Second theory of Axonal Deviation \=

topographic gradient hypothesis (variation of the first theory):

\-axons are sensitive to the same factors but in different amounts

\*diff chemicals + the concentration of the chemicals matter (determined by position of neuron in the matter),

\-Exposure to factors is determined by the relative position of the axons in the tissue (eg. retina),

\-Cell A releases chemical + Axon B and Axon C are both sensitive to chemical

\-However, axon B is exposed to more chemical + Axon B grows toward cell A but axon C does not

\*depending on the position = different chemicals exposed to, diff neurons grow to diff ways b/c diff chemical factors to which the neurons are sensitive and the amount of the chemical will influence where it goes

Synapse formation

\-Synaptogenesis (making new synapses) occurs next, but is less well understood ,

\-Role of glial cells (eg. astrocytes) important,

\-Astroglia for development of synapses = help them form,

\-You form more synapses than you need originally,

\-A lot generated but then are cut down,

\-Many synapses created are later removed (in a massive "synaptic elimination" phase),

\-More meaningful synapses is better - not just more synapses in general

Neuromuscular junction (connection between nerve and muscle fiber)

→ Synapse elimination: An axon may "lose" at some synapses, but "win" at others,

\-The inputs of a mature neutron are fewer but more elaborate and more effective (ie. stronger b/c they are more meaningful

\*polyneuronal innervation of immature muscle (early in development)

What if synapses aren't formed?

When two cells are connected via a synapse, they exchange chemical signals

\-This form of signalling is vital to cell survival

\-Cells that do not form synapses will often die

\-Cell death is normal (You generate more neurons than needed (50% more),

\-Many neurons are lose during development

\-The neuron that survive, you keep for a long time

\*loss of synapses and cells = in context of prenatal = very good, In most of the CNS, new neurons are not generated

Neuronal death in the SC

Under normal conditions, many motor neurons in thee spinal cord die (50%)

\-Removing limb buds increases rate of neuronal death

\*if remove one, fewer neurons survive

\-Adding limb buds decreases rates neuronal death

\-More incentive to keep the cells alive - more likely to develop connections

Apoptosis vs necrosis

Apoptosis is a form of "programmed cell death": Cleaner process, wherein the cell's contents are packaged for convenient disposal, Less inflammation, \*preferable

vs

Necrosis, another form of cell death (eg. via nutritional insufficiency) the results are different: Cells "break apart" + spill their contents, More risk for inflammation, Microglia plays an important role in mitigating inflammation and "cleaning up the mess"

What are the survival signals?

Neurotrophins are transmitted via retrograde signalling (from cell B > cell A)

\-There is a limited amount of neurotransmitters released, which leads to a competition among terminals (NT hypothesis)

\*only certain neurons closest to signal, are the ones that survive

Examples of NTs

\*survival signals and affect phenotype

Four main factors: nerve growth factor (NGF), brain-derived neurotrophic growth factor (BDNF), and neurotrophin-3 and neurotrophin-4 (NT-3, NT-4)

= These compounds can act on tyrosine kinase (Trk) receptors (igh affinity) or p75 receptors (low affinity)

\*retrograde signalling does more than just regulate cell survival \*signalling determines NT phenotype

In mouse brain \= similar order of events in the human brain

Don't myelinate a neuron until it has grown toward its target

\*synapse formation, elimination and cell death continue well after you are born

Periods of Postnatal development:

1. Synaptic density (Synaptic formation, Highlight on synaptic pruning)
2. Developmental periods (Critical and sensitive)
3. Neurogenesis (generation of new cells) (Potential role in learning + memory)

From birth to adulthood....

Volume of the brain quadruples (x4): growth due to synaptogenesis, dendritic arborization, myelination of axons

Growth not due to a gain in neurons (in fact many neurons are lost)

but other processes

Some brain areas develop faster than others

Primary sensory cortices (eg. visual, auditory) develop early (associated w/ vital survival functions for infants), Prefrontal cortex (PFC) develops last

1 - synaptic density w/ age

Regulate behaviour after a certain amount of time → tied to the development of prefrontal cortex

\*prefrontal and visual cortex have different trajectories

Consequences of PFC development:

PFC is involved in planning, initiation, and inhibition of behaviour (and thereby impulse control)

\-These functions are most developed at age 25 (and are often poorly developed beforehand)

\-Don't have the efficient connection still

\-Development of the PFC with time + experience may explain the striking behaviour differences between adolescents and adults

\-Alterations in PFC developmental trajectory may delay - or impair - executive function

\*still give it some skepticism

Synapse elimination

Glial cells play an important role in synapse formation, elimination and maintenance

\-Increasingly, we are considering the role that glial cells might play in disorders of the NS

\*Synaptic density is affected by life experiences (eg. learning)

2 - developmental period

Critical period: time interval where an experience must occur for proper developmen

\-If doesnt occur → then never get normal growth

\-Sensitive period: time interval where an experience has a relatively greater effect on development

\-Thought to be periods of high neuroplasticity; We can identify potential developmental periods with deprivation and enrichment studies (learning) in animals; Periods in humans suggested by correlational data \*for change in synapse number

\*synapse number goes up and then down

Critical period: example

In animals, early visual deprivation (eg. via blindfolding when young) disrupts the development of visual pathways (eg. lateral geniculate axons)

\-If put blindfold → system develops abnormally, need that stimuli early to get the development (especially important for sensory systems)

\-Effects of early visual deprivation cannot be reversed by alter experiences (even if you remove the blindfold)

In contrast to deprivation ...

We have environmental enrichment

CNS changes w/ enrichment

Changes in vascular tissue + astrocytes may also contribute

Why do critical periods end?

Many theories

\-several are focused on axons

\*younger = plasticity (changes more and better than older brain)

\-Myelination of axons occurs after critical periods close = Myelination of existing neurons creates a physical barrier to growth and sprouting of other axons'

\-Not easy to add new ones b/c ones are already there (for developed brain)

\-Myelination can also release certain factors which inhibit axonal growth, such as Nogo

\*lack of certain growth chemicals in the adult brain + inhibitory factors to prevent growth

\*ie. Sensitive periods for language

\*But not entirely a biological phenomena

3 - Adult Neurogenesis

For the most part, the CNS has limited regenerative capacity

\-Neurons once lost are lost forever (and we're losing them all the time)

\-You can only really make new neurons in large amounts during development - we are thus continuously running out of cells

\-However, there may be exceptions to this rule \*some areas of mammalian brain that has new neurons that are made

Adult neurogenesis

This process whereby new neurons are generated in adulthood

\-Thought to occur in two main areas in mammals

\*hippocampus (memory, anxiety) + lateral ventricles

\*it takes time for neurons to develop → making small amounts of cells, but not immediately important (at 6 weeks = integrated into circuits)

The neurogenesis debate

Occurs in most mammalian species studied - but it is currently unclear weather the extent is significant enough to be meaningful in adult humans (most argue that there are low levels later - very low),

\

Assuming it does occur in humans, why does it matter?

Learning + mood regulation

Why does neurogenesis matter?

When young, new adult born neurons have enhanced excitability and plasticity relative to older, developmentally-generated cells

\-Enhanced hippocampal neurogenesis is correlated with improved memory and reduced anxiety

\-Young neurons may play a role in stress resilience (neurogenesis is intact), allowing for greater resistance to stress-induced depression

NDDs

Disorders wherein there is abnormal development of the NS, leading to abnormal cognition and behaviour (starts early),

\-Often emerge early in life (eg. autism, ADHD, intellectual disabilities and language disabilities): High heritability, strong role of genetic factors,

\-Are considered distinct from acquired disorders, which usually emerge in adulthood and are the result of brain changes (eg. injuries) in adulthood: Traumatic brain injury, alzheimer's disease, multiple sclerosis and more

Schizophrenia (SZ)

Symptoms are positive and negative,

Negative = decrease in emotional range, poverty of speech, loss of interest or drive (Flattened affect, alogia, avolution

Positive = hallucinations, delusions, disorganized speech and behaviour (Auditory hallucinations, disorganised speech, delusions, disorganized behaviour)

Others = depression, neurocognitive deficits

Neural features

\-Cortical atrophy/gray matter loss (temporal cortex, HPC and PFC)

\-Abnormal cell organization (HPC)

Hypofrontality

\-Alterations in DA transmission, Treated by drugs that affect the DA system

Major risk factors

Prenatal and postnatal risk factors; some are "choices" (eg. drugs) whereas others are "random accidents" (eg. illness)

A major factor worth discussing is cannabis -

Cannabis during development (correlational): Heavy cannabis use during adolescence is a concern as it may impede brain development during a vital sensitive period; Cannabis use is associated with increased risk for SZ (2x) and an earlier onset,

\-Other drugs might be involved (nicotine/smoking)

\-Earlier onset of cannabis use is associated with more significant impairments in cognitive functioning