PHYSIOLOGY OF BASAL GANGLIA Prof Sultan Ayoub Meo

PHYSIOLOGY OF BASAL GANGLIA Prof. Sultan Ayoub Meo MBBS, M. Phil, Ph. D (Pak), Med Ed, (Dundee), FRCP (London), FRCP (Dublin), FRCP (Glasgow), FRCP (Edinburgh) Prof. Department of Physiology College of Medicine, King Saud University

Lecture Objectives • Enumerate different nuclei of basal ganglia • Know different neurotransmitters that have a role in basal ganglia functions • Appreciate general functions of basal ganglia • Physiological basis of basal ganglia disorders

BASAL GANGLIA: NUCLEI Five nuclei : q Caudate Nucleus q Putamen q Globus Pallidus – external & internal segments. q Subthalamic Nucleus q Substantia Nigra- pars compacta, reticulata Basal ganglia: A group of nuclei, act as a unified functional unit. Basal ganglia: A subcortical nuclei of grey matter located in the interior part of cerebrum / base of the forebrain connected with cerebral cortex, thalamus, and other brain areas. Play a role in action selection, decision of possible behaviors to execute at a given time 3

BASAL GANGLIA: NUCLEI 4

BASAL GANGLIA: NUCLEI 5

Basal ganglia Input 1. Parietal cortex (primary and secondary somatosensory information, secondary visual information), 2. Temporal cortex (secondary visual and auditory information), 3. Cingulate cortex (limbic and emotional status information), 4. Frontal cortex (primary and secondary motor information), 5. Prefrontal cortex.

Basic Circuits of basal ganglia Motor loop (putamen circuit): Learned moment. Cognitive loop (Caudate circuit): Cognitive control of sequences of motor pattern. Mainly it is concerned with motor intentions. (Cognition means thinking process using sensory input with information already stored in memory. ) Limbic loop: Giving motor expression to emotions like, smiling, aggressive or submissive posture. Occulomotor loop: Voluntary eye movement (saccadic movement) 7

Motor loop (putamen circuit): Concerned with learned moment. Putamen circuit is inhibitory. Executes skilled motor activities for example cutting paper with a scissor, hammering on nail, shooting a basket ball & like throwing a base ball. 8

Cognitive loop (Caudate circuit): Concerned with cognitive control of sequences of motor pattern. Motor intentions (Cognition means thinking process using sensory input with information already stored in memory) 9

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Neurotransmitters of basal ganglia 11

Neurotransmitters of basal ganglia Dopamine pathway: From substantia nigra to caudate nucleus and putamen. Gama amino butyric acid pathway: From caudate nucleus and putamen to globus pallidus and substantia nigra. Acetylcholine pathway: From cortex to the caudate nucleus to putamen. Glutamate: Provide the excitatory signals that balance out the large no. of the inhibitory signals transmitted specially by the dopamin, GABA & serotonin inhibitory transmitters. Dopamine: excites areas of caudate/putamen with D 1 receptors to promote the direct pathway, inhibits areas of caudate/putamen with D 2 receptors to inhibit the indirect pathway 12

Dopamine: Neuromodulatory neurotransmitter, excites areas of the caudate/putamen with D 1 receptors to promote the direct pathway, inhibits areas of the caudate/putamen with D 2 receptors to inhibit the indirect pathway Glutamate: Excitatory neurotransmitter Subthalamic nucleus projects glutamate to stimulate the ventrolateral thalamus. Ventrolateral thalamus projects glutamate to stimulate the primary localized motor cortex GABA: Inhibitory neurotransmitter: Caudate/Striatum (direct) projects GABA to inhibit the Gp i GPi projects GABA to inhibit the ventrolateral nucleus Caudate/Striatum (indirect) projects GABA to inhibit the GPe projects GABA to inhibit the subthalamic nucleus

Direct Excitatory Cerebral cortex Prefrontal, premotor, primary motor area, somatosensory area Thalamus Caudate nucleus Indirect Inhibitory Putamen Via globus pallidus subthalamic nucleus 14

RED: Excitatory glutamatergic pathways, BLUE: Inhibitory GABAergic pathways, Magenta: Modulatory dopaminergic pathways GPe: globus pallidus external; GPi: globus pallidus internal; STN: subthalamic nucleus; SNc: substantia nigra compacta; SNr: substantia nigra reticulata 15

Cortex (stimulates) → Striatum (inhibits) → "SNr-GPi" complex (less inhibition of thalamus) → Thalamus (stimulates) → Cortex (stimulates) → Muscles, → (hyperkinetic state) Cortex (stimulates) → Striatum (inhibits) → GPe (less inhibition of STN) → STN (stimulates) → "SNr-GPi" complex (inhibits) → Thalamus (stimulating less) → Cortex (stimulating less) → Muscles, → (hypokinetic state) 16

FUNCTIONS OF BASAL GANGLIA n Voluntary motor activities n Regulatory n Procedural learning n Routine behaviors (Habits) 17

FUNCTIONS OF BASAL GANGLIA 2. Regulatory 1. Voluntary motor activities Plan, Programming Cognitive (thinking) Initiate Emotional functions Maintain (Tone) Voluntary control of eye movement 3. Procedural learning 4. Routine behavior ( habits) 18

Functions 1. Planning & programming (discharge before movement begins ). 2. Motor control of the final common pathway. 3. Muscle tone (lesion increases). 4. Cognitive functions (Frontal cortex) Lesions disrupt performance. 5. Speech , lesion of left caudate results in disturbed speech dysarthria. 19

Metabolic characteristics n n High Copper content. Wilsons disease (Copper intoxication): Ceruloplasmin is low, Lenticular degeneration. 20

Disorders of movement in Basal ganglia disease 1. Hyperkinetic: Excessive abnormal movement i. e. chorea, athetosis, ballism 2. Hypokinetic: Slow movements i. e. akinesia, bradykinesia. 21

HYPERKINESIA Chorea: Rapid involuntary “ dancing” movements Athetosis: Continuous , slow writhing movements. Ballism (Hemiballismus): Involuntary flailing , intense and violent movements 22

HYPOKINESIA Akinesia: Difficulty in initiating movement Braykinesia : Slowness of movement. 23

Parkinson’s disease: Paralysis Agitans Parkinson 1. Slow degeneration / loss of dopaminergic nigrostriatal neurons (60 -80 %). 2. Phenthiazines(tranquilizers drugs). 3. Methyl-Phenyl-Tetrahydro-Pyridine Toxic to SN. (MPTP). 24

Features Tremors: The tremor most apparent at rest Rigidity: Simultaneous contraction of flexors and extensors, which tends to lock up the limbs. Rigidity agonists and antagonists ( spacticity). Lead-pipe rigidity; cogwheel catches (mixture of tremer and rigidity) Akinesia –Bradykinesia: Movements (swinging of arms during walking. Facial expression is masked. Bradykinesia, or "slow movement", is a difficulty initiating voluntary movement, as though the brake cannot be released 25

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Features 27

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Pathogenesis Excitation imbalance Inhibition loss of dopamine inhibition of putamen increases in inhibitory output to GBes decreases inhibitory output of STN increases excitatory output GBis increases inhibitory output to thalamus reduces excitatory drive to cerebral cortex 29

Parkinson’s Disease: Treatment(FYI) n Drug Therapy n n n L-DOPA Cholinergic Pallidectomy Electrical stimulation of Globus pallidus Tissue transplants 30

Huntington’s Disease (Chorea) n Rare n onset 30 -40 s n n Degeneration of Striatum n n n early as 20 s Caudate Putamen GABA & ACh neurons 31

Huntingtons Disease Hereditary , autosomal dominant. Disease of caudate & putamen. Jerky movement of hands toward end of reaching an object. Chorea Slurred speech and incomprehensive. Progressive Dementia 32

Huntingtons Disease Loss of GABA – Cholinergic neurons. Loss of GABAergic neurons leads to chorea Loss of Dopaminergic neurons leads to Parkinson's disease. 33

Summary of functions of basal ganglia n n It play important motor function in starting and stopping motor functions and inhibiting unwanted movement. It changes the timing and scales the intensity of movements. Putamen circuit is inhibitory. Executes skilled motor activities for example cutting paper with a scissor, hammering on nail, shooting a basket ball & like throwing a base ball. Putamen circuit has indirect connection to cortex via thalamus. while caudate has direct connection to the cortex from thalamus. 34

Summary of functions of basal ganglia Caudate circuit is excitatory, has instinctive function which works without thinking and need quick response. eg. response after seeing a lion. [Note: effects of basal ganglia on motor activity are generally inhibitory. ] Lesions of the basal ganglia produce effects on contra lateral side of the body Damage to basal ganglia does not cause paralysis. However it results in abnormal movements n 35

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