Basal Ganglia Masses of gray matter found deep within the cortical white matter Masses of gray matter found deep within the cortical white matter Composed of three parts Composed of three parts Caudate nucleus Caudate nucleus The putamen and the globus pallidus (The lentiform nuclei) The putamen and the globus pallidus (The lentiform nuclei) Fibers of internal capsule running between and through caudate and lentiform nuclei Fibers of internal capsule running between and through caudate and lentiform nuclei

Basal Ganglia Putamen Globus Pallidus

The basal nuclei (ganglia) have an inhibitory role in motor control

Act by modifying ongoing activity in motor pathways Act by modifying ongoing activity in motor pathways Inhibit muscle tone (proper tone – balance the excitatory and inhibitory inputs to motor neurons that innervate skeletal muscle) Inhibit muscle tone (proper tone – balance the excitatory and inhibitory inputs to motor neurons that innervate skeletal muscle) Select and maintain purposeful motor activity while suppressing unwanted patterns of movement (Action Selection: behavioral switching or decision making) Select and maintain purposeful motor activity while suppressing unwanted patterns of movement (Action Selection: behavioral switching or decision making) Monitor and coordinate slow and sustained contractions, especially those related to posture and support Monitor and coordinate slow and sustained contractions, especially those related to posture and support Regulate attention and cognition Regulate attention and cognition Control timing and switching Control timing and switching Motor planning and learning Motor planning and learning Functions of Basal Ganglia

The basal ganglia are a collection of interconnected areas deep below the cerebral cortex. They receive information from the frontal cortex about behavior that is being planned for a particular situation. In turn, the basal ganglia affect activity in the frontal cortex through a series of neural projections that ultimately go back up to the same cortical areas from which they received the initial input. This circuit enables the basal ganglia to transform and amplify the pattern of neural firing in the frontal cortex that is associated with adaptive, or appropriate, behaviors, while suppressing those that are less adaptive. The neurotransmitter dopamine plays a critical role in the basal ganglia in determining, as a result of experience, which plans are adaptive and which are not. Evidence from several lines of research supports this understanding of the role of basal ganglia and dopamine as major players in learning and selecting adaptive behaviors. In rats, the more a behavior is ingrained, the more its neural representations in the basal ganglia are strengthened and honed. Rats depleted of basal ganglia dopamine show profound deficits in acquiring new behaviors that lead to a reward. Experiments pioneered by Wolfram Schultz, M.D., Ph.D., at the University of Cambridge have shown that dopamine neurons fire in bursts when a monkey receives an unexpected juice reward. Conversely, when an expected reward is not delivered, these dopamine cells actually cease firing altogether, that is, their firing rates “dip” below what is normal. These dopamine bursts and dips are thought to drive changes in the strength of synaptic connections—the neural mechanism for learning—in the basal ganglia so that actions are reinforced (in the case of dopamine bursts) or punished (in the case of dopamine dips)

Humphries MD, Gurney KN (2002) The role of intra-thalamic and thalamocortical circuits in action selection, Network 13: We embed our basal ganglia model into a wider circuit containing the motor thalamocortical loop and thalamic reticular nucleus (TRN). Simulation of this extended model showed that the additions gave five main results which are desirable in a selection/switching mechanism. First, low salience actions (i.e. those with low urgency) could be selected. Second, the range of salience values over which actions could be switched between was increased. Third, the contrast between the selected and non-selected actions was enhanced via improved differentiation of outputs from the BG. Fourth, transient increases in the salience of a non-selected action were prevented from interrupting the ongoing action, unless the transient was of sufficient magnitude. Finally, the selection of the ongoing action persisted when a new closely matched salience action became active. The first result was facilitated by the thalamocortical loop; the rest were dependent on the presence of the TRN. Thus, we conclude that the results are consistent with these structures having clearly defined functions in action selection.

Connectivity between different sections BG anatomy ? اتصالات داخلی Basal ganglia: مسیرهای glutamate با رنگ قرمز، مسیرهای dopamine با رنگ صورتی و مسیرهای GABA با رنگ آبی نشان داده شده‌اند.

External pathways

1. Direct pathway: 1. Direct pathway: ♦ Inhibition of internal GP so no longer keeps thalamus from exciting cortex ♦ Facilitate the ongoing action DIRECT

2. Indirect PW: ♦ Causes subthalamus to activate internal GP, suppressing thalamic activation ♦ Suppressing unwanted movements INDIRECT

Parkinson’s disease Damage to Basal Ganglia Parkinson’s disease  Degeneration of DA neurons within the substantia nigra (SN) which project to the striatum.  Under normal circumstances these terminals convert tyrosine to L-dopa which is synthesized to DA. Loss of the pre-synaptic neurons results in  DA release  Possible to lose ~80% of DAergic cells in the SN without manifesting symptoms  Examination of a PD brain reveals loss of SN cells.

Parkinson’s Disease Loss of excitation from substantia nigra to caudate & putamen Results in increased activity in indirect pathway Causes overactivity in the internal GP Inhibits the thalamus, resulting in decreased cortical motor activity INDIRECT

Parkinsons’ Disease: symptoms 1. Akinesia/Bradykinesia: poverty or slowness of automatic and voluntary movements, incl. speech 2. Rigidity: abnormal muscle tone consisting of stiffness (poor range or motion), cogwheeling, spontaneous facial movement 3. Resting tremor: (4-7/sec freq.), referred to as “pill rolling”; may lessen with intentional movement 4. Postural instability: patients often unsteady, may carry centre of gravity out front (falls); difficulty righting 5. Gait disturbance: fixed, stooped posture and shuffling gait 6. Non-motor features may also occur

Parkinson’s Disease: Cognition Symptoms  Bradyphrenia: slowing of thought processes  Memory, specifically retrieving info in nonstructured situations/spatial working memory  Emotional functioning: depression is common  Decrease in executive functioning