BASAL GANGLIA: component and gaba and dopanergic nervous system

Physiology mbbs first year.

1. BASAL GANGLIA DR SUMAN RAI

2. Neural structures involved in the control of movement

3. Basal Nuclei Components Caudate nucleus Substantia nigra Subthalamic nuclei Putamen Globus pallidus

4. Basal Ganglia Neostriatum Caudate nucleus Putamen 2. Paleostriatum Globus pallidus external segment (GPe) Globus pallidus internal segment (GPi) 3. Substantia Nigra Pars compacta (SNc) Pars reticulata (SNr) 4. Subthalamic nucleus (STN)

5. Caudate nucleus + putamen = Corpus Striatum or Neostriatum ( recent parts ) Paleostriatum or pallidum = globus pallidus . Putamen + globus pallidus = lentiform nucleus . ( oldest parts) Globus pallidus = divided in externus and internus Substantia nigra = pars compacta and pars reticulata

6. Basal ganglia contains 2 types of cells

7. Substantial Nigra

8. Input or afferent connections The main afferent connections to basal ganglia terminate in NeoStriatum - All are excitatory ( cholinergic neurons) Receive widespread input from: -all 4 lobes of cerebralcortex ( mainly frontal and parietal lobes) -from all nuclei of thalamus

9. INTER NuclEAR CONNECTIONS DOPAMINERGIC NIGOSTRIATAL PATHWAY GABA- ergic inhibitory striatonigral pathway

10. Dopamine Neuronal System Consists of nigrostriatal fibers From pars compacta of substantia nigra To striatum Dopaminergic Damage of this system causes Parkinson’s disease

11. GABA nergic neuronal system Consists of striatonigral fibres from striatum to substantia nigra gabaminergic neurons Damage causes Huntington’s disease

12. Output Nuclei The main output from the basal ganglia is from the Globus pallidus and Substantia nigra : Projections from globus pallidus to: VA/VL nuclei of thalamus subthalamic nucleus substantia nigra red nucleus of midbrain reticular formation of brain stem Fibers from substantia nigra project to: VA/VL nuclei of thalamus Mostly inhibitory

13. Direct Basal Ganglia Circuit Motor cortex projects to putamen: Excitatory (glutamate) Putamen projects to output nuclei (globus pallidus internus and substantia nigra reticularis): Inhibitory (GABA and substance P)

14. Hypokinetic disorders insufficient direct pathway output excess indirect pathway output Hyperkinetic disorders excess direct path w ay output insufficient indirect path w ay output Motor behavior is determined by the balance between direct/indirect striatal outputs

15. Basal Ganglia Functions Compare proprioceptive information and movement commands. Sequence movements. Regulate muscle tone and muscle force. May be involved in selecting and inhibiting specific motor synergies.

16. Basal Ganglia Functions Basal ganglia are vital for normal movement but they have no direct connections with lower motor neurons. Influence LMNs: Through planning areas of cerebral cortex. Pedunculopontine nucleus of midbrain.

17. Basal Ganglia Functions Basal nuclei set organism’s level of responsiveness to stimuli. Extrapyramidal disorders are associated with basal nuclei pathology: Negative symptoms of underresponsiveness : Akinesias i.e. Parkinson disease Positive symptoms of over-responsiveness: Choreas , athetoses , ballisms i.e. Huntington’s chorea

18. PARKINSON”S DISEASE DEFINITION:- Parkinsons disease results from degeneration of nigrostriatal dopaminergic neurons of basal ganglia.

19. Causes 1) Idiopathic – unknown cause 2) Drugs – Phenothiazine etc. 3) MPP – Methyl – Phenyl pyridium accumulates in the neurons of basal ganglia .

20. Features:- Both hypokinetic and hyper kinetic movements are observed in parkinsonism .

21. HYPOKINATIC MOVEMENTS 1) Akinesia -- Difficulty in initiating movements and decreased spontaneous movements 2) Brady kinesia OR Hypokinesia -- Slowness of movements. 3) Decreased associated movements - Loss of subconcious associated movements . - No swinging of arms while walking. - Face become mask like.

22. HYPERKINETIC MOVEMENTS 1) RIGIDITY 2) TREMORS 3) FESTINATING GAIT

23. Parkinson Disease Purves D, et al. Neuroscience, 5 th Ed., Sinauer Associates, 2012

24. HYPERKINETIC MOVEMENTS 1) RIGIDITY:-- Cause – Increased gamma motor neuron discharge in both agonists and antagonists muscle. LEAD- PIPE RIGIDITY

25. Mechanism OF RIGIDITY :-- Neostriatum excitatory cholinergic inhibitory cholinergic * if dopaminergic neuron decreases, balance shifts towards excitatory effect.

26. 2) TREMORS:- Regular rhythmic alternate contraction of agonist and antagonist muscle at 6-8 times per sec.

27. TREMORS Affects fingers, lips, hand and tounge . Present at rest but disappears during activity. CAUSE:- Degenerative lesion in reticular formation and ascending connection.

28. GAIT Patients walks in an attitude that as if he is trying to catch the center of gravity . - bends forward - takes short steps

29. Treatment 1 ) Dopamine agonists ( Bromoriptine ) are used. 2) Antcholinergic drugs improve the symptoms. 3) Implantation of fetal basal ganglia improve symptoms. 4)transplantation of glomus cells – glomus cell releases dopamine locally.

30. Huntington Disease Autosomal dominant disorder Chromosome 4 – Huntingtin gene Onset age 30 - 50 years of age Initial symptoms chorea and alternation of mood Disease progression – dementia worsening personality changes

31. Huntington’s disease

32. Huntington’s disease Pathophysiology Atrophy of striatum Loss of striatal GABAergic neurons Neuropathological sequence 1 st : loss of striatal GABA/ enkephalin /D2-R neurons ( indirect pathway) 2 nd : loss of striatal GABA/ dynorphin /D1-R neurons (direct pathway) & cortical atrophy

33. Huntington’s disease Cognitive abnormalities Executive function (complex tasks) Recent and remote memory (poor retrieval) Psychiatric changes Depression Psychosis Later decline Immobility Weight loss Death within 10-25 years (often from pneumonia)

34. Huntington’s disease Symptoms Early motor signs chorea (brief, involuntary movements) dystonia (abnormal postures) Choreatic gait Dystonic movements

35. Basal Ganglia resting tremor postural instability festination rigidity masked facies bradykinesia dyskinesia torticollis chorea athetosis hemiballismus akathisia Cerebellum intention tremor dysmetria dysdiadochokinesia hypotonia heal to shin finger to nose rebound ataxic gait titubation nystagmus dysmetric saccades

36. Basal ganglia lesions produce contralateral signs. Cerebellar lesions produce ipsilateral signs.

37. Most movement disorders produced by cerebellar and basal ganglia pathology disappear during sleep. Cerebellar and basal ganglia signs are usually not present if the corticospinal tract is damaged.

38. The BASAL GANGLIA are the autopilot for procedural movements. The CEREBELLUM is the refiner of finely controlled movements (particularly of fingers).

39. The cerebellum is the great comparator: 1. It compares cortical willful command with muscle tension, joint position, & tone (via ipsilateral spinocerebellar tracts) 2. Advises the cortex on how much, how many, how fast 3. The motor cortex sends the revised command down the corticospinal tract

40. THANKS