1. PhD MD MBBS Faculty of Medicine Al Maarefa Colleges of Science & Technology Faculty of Medicine Al Maarefa Colleges of Science & Technology Lecture – 9: Basal Nuclei Nervous System Physiology By Dr. SHAHAB SHAIKH PhD MD MBBS Faculty of Medicine Al Maarefa Colleges of Science & Technology Faculty of Medicine Al Maarefa Colleges of Science & Technology

2. BASAL NUCLEI Basal Nuclei Also known as Basal Ganglia (BG) are a group of nuclei located subcortically. The term BG includes the corpus striatum (caudate nucleus and the lenticular nucleus, which includes the putamen and the Globus Pallidus) and other subcortical nuclei such as the Subthalamic nucleus (STN) and the Substantia Nigra (SN) [consisting of the pars compacta (SNc) and pars reticulata (SNr)]. 2 BG has been implicated in many neurological and psychiatric disorders, including Parkinson's disease (PD), Attention Deficit Hyperactivity Disorder (ADHD), Tourette's syndrome, and dystonias.

3. BASAL NUCLEI - FUNCTIONS Modulation of motor activities through neuronal circuits. Maintain purposeful motor activity while suppressing unwanted or useless movement. Change the Timing and Scale the Intensity of Movements Basal ganglia function in association with the corticospinal system to determine & control complex patterns of motor activity. 3

4. BASAL NUCLEI - FUNCTIONS Regulate muscle tone - Inhibit muscle tone throughout the body Monitor and coordinate slow, sustained contractions related to posture and support. Prevent abnormal involuntary movements. Control group of movements for emotional expression. Role in procedural learning, routine behaviors or "habits" such as bruxism. Role in Memory, emotion, Reward Learning and other cognitive functions. 4

5. BASAL NUCLEI 5 Subthalamic Nucleus Caudate Nucleus Caudate Nucleus Putamen Globus Pallidus Substantia Nigra Lenticular Nucleus Lenticular Nucleus Striatum

6. BASAL NUCLEI 6

7. 7

8. BASAL NUCLEI - CONNECTIONS 8

9. 9 Comes from the cerebral cortex (motor area) and projects to the STRIATUM ( Caudate nucleus & Putamen) MAIN INPUT TO THE BASAL GANGLIA MAIN OUTPUT FROM THE BASAL GANGLIA Is via the thalamus to the cerebral cortex (motor area)

10. 10 THE DIRECT PATHWAY Cortex Striatum "SNr-GPi" complex Thalamus Cortex Muscles (hyperkinetic state) THE INDIRECT PATHWAY Cortex Striatum "SNr-GPi" complex Thalamus Cortex Muscles STN GPe (hypokinetic state) Globus Pallidal neurons operate using a disinhibition principle. These neurons fire at steady high rates in the absence of input & have inhibitory effects on their target (Thalamus).

11. 11 THE DIRECT PATHWAY Cortex BASAL NUCLEI Muscles Cortex (hyperkinetic state) The antagonistic functions of the direct and indirect pathways are modulated by the Substantia Nigra - Pars Compacta (SNc), which produces Dopamine. THE INDIRECT PATHWAY Cortex BASAL NUCLEI Muscles (hypokinetic state) Cortex

12. 12 (STRIATUM)

13. LESIONS OF BASAL GANGLIA Reminder … – Normal muscle tone is maintained by a balance between excitatory and inhibitory input to neurons that innervate skeletal muscle. – Basal Nuclei do not directly influence the efferent motor neuron (alpha and gamma) that cause muscle contraction but modify activity of motor pathways. 13

14. LESIONS OF BASAL GANGLIA Causes two types of Manifestations... 1.Hypokinetic –Increased tone & rigidity –E.g. : Parkinsonism 2.Hyperkinetic –Abnormal involuntary movements - dyskinesia –E.g. : Athetosis, Chorea & Hemiballismus 14

15. Parkinson’s Disease 15 Parkinson’s disease is due to degeneration of dopaminergic neurons from the substantia nigra (Nigro-striate fibres) Clinical symptoms Rigidity – Cogwheel, Lead Pipe Tremor (Resting) – Pill rolling type Hypokinesia/Akinesia - poverty and slowness in initiating and carrying out different motor movement. Face – expressionless, Mask like face Blinking of eyelid is reduced Writing becomes small – micrographic and spidery Changes in posture – Stoop is characteristic Gait – becomes hurrying, festinant, short and shuffling with poor arm swinging

16. Parkinson’s Disease 16 The hallmark of the parkinsonism state is increased neuronal activity in the output nuclei of the BG (GPi/SNr) leading to excessive inhibition of the thalamo-cortical and brain stem motor systems. Dopamine deficiency leads to reduced inhibition of GABAergic striatal neurons in the indirect pathway and decreased facilitation of GABAergic neurons in the direct pathway neurons. Reduced inhibition of neurons in the indirect pathway leads sequentially to over-inhibition of GPe, disinhibition of STN, and increased excitation of GPi/SNr. Decreased activation of neurons in the direct pathway reduces its inhibitory influence on GPi/SNr and contributes to their excessive output activity.

17. Parkinson’s Disease 17

18. Parkinson’s Disease Treatment Levodopa (L-dopa) It is precursor of dopamine L-dopa is converted into dopamine in the brain. Surgical destruction of GP / VL Nu of Thalamus Striatal implants of dopamine containing neurons of fetal origin. 18

19. 19 Lesions of Basal Ganglion

20. References Human physiology by Lauralee Sherwood, 8 th edition Text Book Of Physiology by Guyton & Hall, 11 th edition

21. 21 THANK YOU