Neuro Block 3

motor cortex

part of frontal lobe for planning, initiating, and directing voluntary movements; located in the precentral gyrus; stimulation of neurons causes movements

brainstem centers

parts of brain that control basic movements and posture

basal ganglia

collection of nuclei in the forebrain that control the initiation and termination of voluntary movements (force of movements); receive input from cerebral cortex and provide output to upper motor neurons of the cortex and brainstem

cerebellum

part of brain involved in sensory motor coordination of ongoing movement; topographical organization; important for: balance, coordinated, learned motor skills, accuracy and error correction of movement

upper motor neurons

motor neurons that span from the motor cortex to interneuron circuits in the brainstem or spinal cord; do not leave CNS and do cross the midline; influence lower motor neurons indirectly via spinal interneurons (some do terminate directly); contribute to voluntary movement

lower motor neurons

motor neurons that span from cranial nerve nuclei or spinal cord to muscle; leave the CNS and do not cross over the midline; somata located in the ventral horn of the spinal cord; project to muscles and cause them to contract

alpha motor neurons

lower motor neurons that project to extrafusal muscle fibers (muscle contraction)

beta and gamma motor neurons

lower motor neurons that project to muscle spindles (spindle tension)

motor unit

one alpha motor neuron and all its postsynaptic muscle fibers

neuromuscular junction (NMJ)

consists of the presynaptic boutons of the the motor neuron and the postsynaptic end plate of the muscle fiber

end plate

region on a muscle fiber where a motor axon terminates; specialization of the postsynaptic muscle fiber with membrane "pockets"

junctional folds

pockets in the membrane of the postsynaptic muscle fiber

end plate potential (EPP)

depolarization due to neurotransmitter release that occurs at the "end plate"; graded in proportion to the amount of Ach released

short-term plasticity

a temporary increase or decrease in the EPP amplitude that depends on the firing rate of the alpha motor neuron

mini EPP (mEPP)

smallest end plate potential that can be recorded from one vesicle

myasthenia gravis

autoimmune disease of the NMJ in which the body produces abnormal antibodies that attack and degrade or destroy the AChRs on skeletal muscle; lack of working receptor sites causes the muscle weakness (result of decreased force of muscle contraction); first line treatment is drugs that inhibit the enzyme (acetylcholinesterase) that breaks down acetylcholine at the NMJ

compound action potential

a signal recorded from a nerve trunk made up of numerous axons; result of summation of many action potentials from the individual axons in the nerve trunk

proprioceptors

receptors in the muscles and joints that provide sensory input from the muscles to the spinal cord

muscle spindles

comprised of muscle fibers and sensory afferents; intrafusal fibers receive gamma-motor neuron inputs from the spinal cord; stretching the muscle stretches the intrafusal muscle fibers; activates mechanoreceptors in the sensory afferents causing action potentials that are relayed to the spinal cord

golgi tendon organ reflex

protective circuit that causes the muscle to relax if it is overloaded; sensory inputs activate local neurons that inhibit motor neurons of the same muscle causing muscle relaxation

medial local circuit neurons

neurons that project over many spinal cord segments as well as bilaterally to coordinate left/right and upper/lower body movement as well as posture

lateral local circuit neurons

neurons that project to fewer segments and unilaterally to coordinate fine, independent muscle movements (i.e. finger movements on one hand)

pyramidal decussation

corticospinal tract fibers cross the midline at the level of the medulla

lateral corticospinal tract

projection of upper motor neurons from cerebral cortex down the spinal cord for distal musculature; 90% of descending projections; decussation at the medulla

anterior corticospinal tract

projection of upper motor neurons from brainstem down the spinal cord for proximal musculature; 10% of descending projections; decussation at level where the axons synapse onto lower motor neurons in the ventral horn

superior colliculus

controls movements that orient eyes, head and body toward sensory stimuli

vestibular nuclei

controls reflexive changes in posture and reflexive eye movements

reticular formation

controls anticipatory changes in posture

medial white matter

made up of vestibulospinal, reticulospinal and colliculospinal tracts; coordinates multiple muscle groups by running the full length of the spinal cord and projecting mainly to interneurons rather than directly to lower motor neurons

somatotopic organization

different regions of motor cortex control different parts of the body, such that the body can be "laid out" across the cortex; disproportionate amounts of cortex devoted to different body parts relates to specialization of function: grabbing, tuning, running, etc; largely preserved throughout the descending motor pathways

Betz cells

large pyramidal neurons of the primary motor cortex that synapse directly on spinal cord interneurons and lower motor neurons for the hand

motor homunculus

body map in primary motor cortex; electrical stimulation of the surface of the brain maps locations that elicit specific muscle contractions; body regions that require fine motor control (hands/face) have a lot of cortical representation compared to areas that don't require such fine control

accessory motor areas

higher order parts of brain required for more complicated tasks; more intense stimulation is required than for M1

plasticity

motor maps can change as a result of learning and in response to damage

Purkinje cells

main target in cerebellum from inputs; release GABA to inhibit neurons of the cerebellar nuclei

climbing fibers

cell bodies located in inferior olive (inferior olivary nuclei); axons project to Purkinje cells and deep cerebellar nuclei; have strong excitatory control over Purkinje cells

mossy fibers

cell bodies located in pons and spinal cord; excite granule cells in cerebellar cortex and neurons in the deep cerebellar nuclei

granule cells

excitatory neurons; stimulated by the mossy fibers; axons form the parallel fibers, which excite Purkinje cells

long term motor learning

ability to modify motor programs with practice in order to improve the effectiveness and efficiency of movements

deep cerebellar nuclei

cells that receive inhibitory input from the cerebellar cortex; sole source of output from the cerebellum

dentate nucleus

deep cerebellar nucleus from lateral cortex of cerebrocerebellum; projects to the thalamus (and then motor cortex) for motor planning

interposed nuclei

deep cerebellar nuclei from intermediate cortex of spinocerebellum

fastigial nucleus

deep cerebellar nucleus from vermis of spinocerebellum; projects to the brainstem upper motor neurons for motor execution

cerebellar peduncles

axon bundles that connect the cerebellum to the rest of the brain

superior peduncle

cerebellar peduncle connected to the midbrain that carries cerebellar output; axons leaving the cerebellum; output to the thalamus which projects to motor cortex (body movements) and output to the superior colliculus (eye movements); decussation level for ascending inputs from the cerebellum to the cortex

middle peduncle

cerebellar peduncle connected to pons that carries cerebellar input; axons entering the cerebellum; decussation level for descending input from the cortex via the pons; projects to cerebrocerebellum;

inferior peduncle

cerebellar peduncle connected to medulla that carries input and output; input from vestibular nuclei and spinal cord, output to the vestibular nuclei

cerebral peduncles

axon bundles carrying cortical movement information to the pons, which then sends this information to the cerebellum through the middle *cerebellar* peduncle; NOT cerebellar peduncles but still an important pathway in the cerebellar circuit

cortical pathway

pathway in and out of cerebellum that selects efficient motor programs (motor planning); impairment can cause difficulties producing skilled sequences of learned movements, such as playing a musical instrument

spinal cord pathway

pathway in and out of cerebellum involved in error correction for proximal and distal muscle movements•; impairment can cause uncoordinated movements of proximal muscles or distal muscles

ataxia

lack of voluntary coordination of muscle movements

dysmetria

overshoot or undershoot target

intention tremor

irregular movement that worsens as movement approaches target; impairment of Purkinje synapses that underlie cerebellar degradation

spinocerebellar ataxia

errors in smoothness and direction of targeting movements; includes dysmetria and intention tremors; caused by genetic disorders

vestibular pathway

pathway in and out of cerebellum that controls muscles used in balance of the body and reflexive eye movements; impairment can cause inability to stand upright and not maintain the direction of gaze or uncoordinated eye movements

nystagmus

eyes drift from target and then jump back to it

corticostriatal pathway

sensory and motor input from multiple cortical regions to the caudate and putamen

nigrostriatal pathway

dopaminergic input from substantia nigra pars compacta to the caudate and putamen; SNc provides dopaminergic input to the corpus striatum, which excites the direct pathway, inhibits the indirect pathway

globus pallidus

receives input from the putamen and caudate; contains external and internal divisions; one of the main outputs from the basal ganglia to other parts of the brain; inhibits the thalamus (important for body movements) and therefore motor cortex

substantia nigra pars reticulata

receives input from the caudate; inhibits the superior colliculus (important for eye/head movements)

striatum

part of basal ganglia containing caudate nucleus and putamen

medium spiny neurons

GABAergic inhibitory neurons in the basal ganglia that receive input from cortex and SNc and inhibit neurons in the Globus Pallidus (GP) & SNr; do not fire action potentials easily, require many cortical inputs; fire action potentials before movement; code a "decision to move toward a goal" rather than movement itself.

global pallidus neurons

each one receives input from ~ 100 medium spiny neurons; required to ensure initiation of the correct motor plan; inhibited by GABA from MSNs

disinhibition

2 sequential inhibitions lead to activation of the pathway

direct pathway

cortical input to the basal ganglia excites MSNs in the Caudate and Putamen which inhibit neurons in the Globus Pallidus or Pars Reticulata and disinhibit the thalamus or superior colliculus to promote movement

indirect pathway

counteracts the direct pathway to terminate movement or suppress unwanted movements by increasing the inhibitory influence of the internal globus pallidus

hyperdirect pathway

counteracts the direct pathway to modulate movement through the subthalamic nucleus

D1

excitatory (depolarizing) dopaminergic receptors in the striatal neurons of the direct pathway; increase disinhibition of the thalamus, allowing movements to occur

D2

inhibitory (hyperpolarizing) dopaminergic receptors in the striatal neurons of the indirect pathway; prevent inhibition of the thalamus, allowing movements to occur

Parkinson's disease

loss of dopaminergic neurons in nigrostriatal pathway; symptoms occur when ~80% of SNc neurons are gone; death in 10-20 yrs and also dementia in later stages; symptoms include resting tremor, rigidity, loss of voluntary movement, shuffling gait, and disturbed posture; caused by genetic susceptibility, toxins, pesticides, and head trauma

hypokinetic symptoms

decreased voluntary movement

bradykinesia

slowed movements due to muscle rigidity

biogenic amines

dopamine(DA), norepinephrine (NE), epinephrine (Epi), serotonin (5-HT), histamine; involved in many behavioral functions; also found in the peripheral nervous system; can play a role in psychiatric diseases

dopamine

catecholamine involved in initiation of movement (basal ganglia) and motivation, reward, reinforcement (substantia nigra and ventral tegmental area); receptors are affected by cocaine and amphetamine; multiple types of receptors (D1-D5), all of which are metabotropic

vesicular monoamine transporter (VMAT)

transports monoamines into secretory vesicles using proton gradients; structure: twelve transmembrane domains; inhibitors: reserpine and tetrabenazine; regulations: trafficking, dimerization; includes VMAT2 and SLC18A2

Levodopa

dopamine precursor converted into dopamine in the brain and released by remaining dopamine neurons; used as Parkinson's disease treatment; issues are that necessary high doses cause nausea and vomiting and long-term, can cause involuntary movements and on/off period of drug working

carbidopa

enzyme that delays the conversion of levodopa to dopamine; does NOT cross the blood-brain barrier; allows more levodopa to get to the brain, so lower doses are required; produced a significant improvement in the treatment of PD; reduces nausea and vomiting associated with high doses of levodopa but other side effects are still present

Lewy body

abnormal circular structures with a dense core consisting of alpha-synuclein protein; found in the cytoplasm of nigrostriatal neurons in people with Parkinson's disease

alpha-synuclein

A protein normally found in the presynaptic membrane, where it is apparently involved in synaptic plasticity. Abnormal accumulations are apparently the cause of neural degeneration in Parkinson's disease.

MPTP

neurotoxin that induces Parkinson's disease; precursor to MPP+; model is selective, mitochondrial, only mouse, and no pathology (apoptosis)

deep brain stimulation

implantation of an electrode into areas of the basal ganglia (particularly GPi and STN); stimulation overrides abnormal patterns of basal ganglia activity; requires brain surgery, expensive; may exacerbate depression / emotional symptoms and cause symptoms in those you have not had them previously

brain tissue transplant

fetal tissue, genetically engineered cells that produce dopamine transplanted to patients with Parkinson's disease; still in experimental stage, controversial

Dementia with Lewy Bodies (DLB)

motor symptoms of Parkinson's disease plus orthostatic hypotension, cognitive decline, hallucinations, loss of abstract thinking, fluctuating alertness; pathology: Lewy body inclusions, loss of dopaminergic neurons of the substantia nigra; treatment: no cure, similar treatments as PD for motor symptoms, cognitive symptoms improve with medications used in Alzheimer's

hypokinetic disorders

Parkinsonism, apraxia, catatonia, gait disorders, stiff persons, etc

hyperkinetic disorders

tremor, dystonia, chorea, tics, myoclonus, etc.

Amyotrophic Lateral Sclerosis (ALS)

disease caused by death of upper and lower motor neurons; motor symptoms- muscle weakness, tripping, dropping items, fatigue, slurred speech, muscle cramps; end stage impacts the muscles responsible for breathing which leads to ventilator use; protein inclusions in cell bodies and axons of degenerating neurons

superoxide dismutase

mutation of this gene causes 20% of familial ALS cases

Riluzole

ALS medication that extend the amount of time before ventilation support is needed and it can extend survival by a few months

Dexpramipexole

ALS treatment in its phase III clinical trial; slowed disease progression; increases mitochondrial efficiency

Huntington's disease

autosomal dominant genetic disorder that causes neurodegeneration of striatum; insufficient tonic output from the GP permits unwanted, excessive movements; motor symptoms- lack of coordination, unsteady gait, chorea; cognitive symptoms- executive functioning such as planning, abstract thinking, rule acquisition; connection between the caudate and the GPe is degenerated

huntingtin

Poly-Q repeat (CAG nucleotide repeat that codes for the amino acid glutamine) in the N-terminus of this protein causes Huntington's disease; healthy if < 36 repeats and symptomatic if > 40 repeats

Tetrabenazine

treatment for chorea that depletes stores of monoamines by reversing the vesicular monoamine transporter 2 (VMAT2) on vesicles

tremor

involuntary rhythmic, oscillatory movements; alternating or synchronous contractions of antagonist muscles

essential tremor

autosomal dominant nerve disorder characterized by uncontrollable shaking, or "tremors," in different parts and on different sides of the body; hands, arms, head, larynx, tongue, and chin (rarely lower body) affected; true cause not understood but thought that the responsible abnormal electrical brain activity is processed through the thalamus

homeostasis

active regulation of the body to create a balanced internal environment controlled by the different nuclei of the hypothalamus

infundibulum

stalk that connects the pituitary gland to the hypothalamus

posterior pituitary

extension of the hypothalamus

anterior pituitary

true endocrine gland of epithelial origin

sympathetic stress system

fast response to stress, synaptic signaling and release of epinephrine and norepinephrine

HPA axis stress system

slow response to stress, hormonal signaling and release of cortisol through adrenal glands