Basal GangliaBasal Ganglia

Masses of gray matter found deep within the Masses of gray matter found deep within the cortical white mattercortical white matter

Composed of three partsComposed of three parts Caudate nucleusCaudate nucleus The putamen and the globus pallidus The putamen and the globus pallidus

(The lentiform nuclei)(The lentiform nuclei) Fibers of internal capsule running between and Fibers of internal capsule running between and

through caudate and lentiform nucleithrough caudate and lentiform nuclei

Basal GangliaBasal Ganglia

PutamenGlobus Pallidus

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

Act by modifying ongoing activity in motor pathwaysAct by modifying ongoing activity in motor pathways

Inhibit muscle tone (proper tone – balance the excitatory Inhibit muscle tone (proper tone – balance the excitatory and inhibitory inputs to motor neurons that innervate and inhibitory inputs to motor neurons that innervate skeletal muscle)skeletal muscle)

Select and maintain purposeful motor activity while Select and maintain purposeful motor activity while suppressing unwanted patterns of movement suppressing unwanted patterns of movement (Action Selection: behavioral switching or decision making)(Action Selection: behavioral switching or decision making)

Monitor and coordinate slow and sustained contractions, Monitor and coordinate slow and sustained contractions, especially those related to posture and supportespecially those related to posture and support

Regulate attention and cognitionRegulate attention and cognition

Control timing and switchingControl timing and switching

Motor planning and learningMotor planning and learning

Functions of Basal GangliaFunctions 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 13:131-56

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

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Basal اتصاالت داخلی ganglia مسیرهای :

glutamate با رنگ قرمز، مسیرهای

dopamine با رنگ صورتی و مسیرهای

GABA با رنگ آبی اند. نشان داده شده

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

Damage to Basal Ganglia Parkinson’s diseaseParkinson’s disease

Degeneration of DA neurons within theDegeneration of DA neurons within the substantia nigra (SN) which project to the striatum. substantia nigra (SN) which project to the striatum.

Under normal circumstances these terminals convertUnder normal circumstances these terminals convert tyrosine to L-dopa which is synthesized to DA. tyrosine to L-dopa which is synthesized to DA. Loss of the pre-synaptic neurons results in Loss of the pre-synaptic neurons results in DA releaseDA release

Possible to lose ~80% of DAergic cells in the SN withoutPossible to lose ~80% of DAergic cells in the SN without manifesting symptoms manifesting symptoms

Examination of a PD brain reveals loss of SN cells.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: symptoms1. 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

SymptomsSymptoms

Bradyphrenia: slowing of thought processesBradyphrenia: slowing of thought processes

Memory, specifically retrieving info in nonstructuredMemory, specifically retrieving info in nonstructured situations/spatial working memory situations/spatial working memory

Emotional functioning: depression is commonEmotional functioning: depression is common

Decrease in executive functioningDecrease in executive functioning