Basal Ganglia.pdf

17 March 2024 12:43 Main Ideas Notes Concepts & Keywords: 1. Subcortical Nuclei: Basal Ganglia (BG) are a collection of subcortical nuclei, crucial for regulating motor function and behaviours. 2. Excitatory & Inhibitory Connections: These nuclei are connected through a complex circuit of excitatory...

17 March 2024 12:43 Main Ideas Notes Concepts & Keywords: 1. Subcortical Nuclei: Basal Ganglia (BG) are a collection of subcortical nuclei, crucial for regulating motor function and behaviours. 2. Excitatory & Inhibitory Connections: These nuclei are connected through a complex circuit of excitatory and inhibitory synapses, determining the flow of motor commands. 3. Motor Loop: BG's motor loop involves multiple pathways including the direct, indirect, and hyperdirect pathways, influencing movement execution and inhibition. 4. Dopaminergic Modulation: The nigrostriatal pathway, involving dopamine from the substantia nigra, modulates the activity of the direct and indirect pathways. 5. Movement Disorders: Dysfunctions in BG circuits are linked to movement disorders like Parkinson’s disease, highlighting its role in movement regulation. 6. Parallel Loops: BG consists of multiple parallel loops, each with distinct functions but similar architecture, integrating motor, cognitive, and emotional processes. 7. Reward & Motivation: BG is involved in reward signalling and motivation, influencing behavior based on positive reinforcement and expected outcomes. 8. Deep Brain Stimulation (DBS): A treatment for movement disorders, DBS modulates BG activity through targeted electrical stimulation, improving symptoms of disorders like Parkinson's disease. 9. Habit Formation: BG plays a role in transforming goal-directed actions into habits, a process influenced by dopaminergic signalling. Notes Studies 1. Optogenetic Studies (G Cui et al., Nature, 2013): Demonstrated that both direct and indirect pathways of BG are activated during movement, challenging the classical view of their exclusive roles. This suggests a more nuanced understanding of how movements are initiated and controlled. 2. Deep Brain Stimulation Reviews (Volkmann, 2004; Breit et al., 2004): Highlighted the effectiveness of DBS in treating Parkinson's disease, offering insights into the underlying mechanisms of BG circuits and their role in movement disorders. 3. Reward Signalling (Graybiel, 2005; PMID: 16271465): Reviewed the role of dopamine in BG as a signal for unexpected rewards, shaping behavior through reinforcement learning. This work underscores the importance of BG in not just motor control but also in reward -based learning and decision -making. 4. Model-Free Habitual Learning in Mice (PMID: 26189204): Investigated the role of corticostriatal plasticity in forming habits, demonstrating that repetitive actions become more stereotyped through learning, highlighting the BG's role in transitioning from goal-directed to habitual actions. 5. Goal-Directed Actions and Cortico -BG Loop (PMID: 22388818): Showed how mice can learn to control sounds for rewards without physical movement, suggesting goal -directed actions are supported by the cortico -BG loop. This implies the BG's involvement in complex decision -making processes beyond simple motor control. Notes Theoretical Models: The balance between direct and indirect pathways is crucial for initiating or inhibiting movements. Abnormalities in these pathways lead to either hyperkinetic or hypokinetic movement disorders. Dopamine's role extends beyond movement control to include motivation and reward processing, influencing how actions are selected and performed based on expected outcomes. Implications for Research & Treatment: Understanding the intricate workings of BG can inform treatments for movement disorders, such as Parkinson's disease, through interventions like pharmacotherapy and DBS. Insights into the reward-related functions of BG can guide approaches for addressing motivational aspects of neurological disorders and potentially addictive behaviors. Extra: Motivation for action Linking limbic and motor loops at the striatal medium spiny neuron The inputs from cortex to striatum follow a precise organisation: ○ Sensorimotor Cortex-> striatal matrix (mostly putamen) ○ Limbic Cortex-> striosome (mostly caudate nucleus) Striatal MEDIUM SPINY NEURON (MSN) ○ Respond to cortical input is filtered by motivational drive ○ Motivation transmitted by limbic striatum, and midbrain (SNc) DA neurons Different locations of converging sensorimotor and motivational inputs onto MSN dendritic spines allows motivation to filter how information flows through the BG sensorimotor loop, making a given action more or less likely Circuit physiology and clinical movement disorders Given the excitatory/inhibitory circuit of the BG - expect BG disease to involve excessive movement or insufficient movement BG diseases can be classified as hypokinetic (deficiency in movement) or hyperkinetic (excess of movement) movement disorders 10. Learning & Plasticity: Corticostriatal plasticity in BG supports learning and adaptation of actions based on reinforcement history and outcomes. Easy-to-Understand Language Summaries: The Basal Ganglia (BG) are like the brain's conductor, directing when and how to move or not to move, and helping form habits. BG's circuits are super highways of signals, with some paths green-lighting actions and others stopping them in their tracks. Think of dopamine as the BG's fuel, boosting pathways that help you move smoothly and dampening those that don't. If the BG gets out of tune, movements can become too slow, too fast, or unwanted, leading to conditions like Parkinson's disease. DBS is like a pacemaker for the brain, sending electrical pulses to help control movements when the BG's signalling goes awry. Beyond just moving us, BG helps decide which actions are worth repeating by giving us a sense of reward, guiding us towards beneficial behaviors. Learning for BG is like updating its software, constantly adjusting which actions are rewarded and becoming more efficient over time. Studies using cool tech like optogenetics (light to control cells) show us how complex and integrated these brain circuits are, challenging old theories and paving the way for new treatments. Whether it's choosing to eat a cookie or deciding to exercise, the BG plays a role in shaping our actions based on past rewards and future goals. Summary Understanding the BG isn't just about treating diseases; it's also about unlocking the secrets of how we learn, make decisions, and form habits. PSYC0032 The Brain in Action Page 1 Parkinson's disease: treatment I Symptoms appear only when 70% of nigrostriatal dopaminergic neurons have already died Levodopa treatment (precursor of dopamine) ○ restored motor function ○ reduced bradykinesia ○ decreased rigidity Side effects: dyskinesias ○ Impulse control disorders Notes PSYC0032 The Brain in Action Page 2