L11 NEUR3101 Basal ganglia 1 slide per page.pdf

NEUR3101 Motor control Lecture 11 Basal ganglia A/Prof Ingvars Birznieks Chapter 18, Modulation of the movement by the basal ganglia. Purves et. al, Neuroscience (6th Ed) The basal ganglia are involved in regulation of wide range of motor and non-motor functions...

NEUR3101 Motor control Lecture 11 Basal ganglia A/Prof Ingvars Birznieks Chapter 18, Modulation of the movement by the basal ganglia. Purves et. al, Neuroscience (6th Ed) The basal ganglia are involved in regulation of wide range of motor and non-motor functions Box 18D  Introduction to the basal ganglia The term basal ganglia refers to a functionally diverse set of nuclei that lies deep within the cerebral hemispheres. The subset of these nuclei relevant for motor function are caudate putamen STRIATUM globus pallidus (GP) Structures closely associated with the motor control loops of basal ganglia subthalamic nucleus substantia nigra compacta (dopaminergic neurons) ventral anterior and ventral lateral (VA/VL) nuclei of thalamus Oculomotor loop: substantia nigra reticulata (inhibitory output neurons) superior colliculus ventral anterior and mediodorsal nuclei of thalamus Coronal section Figure 18.1 Introduction to the basal ganglia STRIATUM = caudate + putamen  Function of the basal ganglia Cerebral cortex + Basal ganglia control loops - Thalamus Basal ganglia do not project directly to upper and lower motor neurons or local circuit neurons. The control loops operating between basal ganglia, thalamus and cortex are responsible for smooth switching between commands that initiate a movement and those that terminate the movement. At rest the basal ganglia tonically inhibit thalamus. Movement can be initiated after removing those inhibitory inputs.  Function of the basal ganglia Thalamus VA/VL/MD Spontaneous activity in basal ganglia inhibits thalamus Thalamus Basal ganglia VA/VL/MD In response to various inputs basal ganglia selectively remove or increase inhibition to neurons in thalamus responsible for different movements Basal ganglia Thalamus VA/VL/MD Indirect pathway Unwanted movement Direct pathway Desired movement Indirect pathway Unwanted movement  Circuits of the basal ganglia Inputs to striatum Medium spiny neurons in putamen must be simultaneously stimulated by many excitatory inputs from cortical and nigral neurons to become active. Neurons in the putamen tend to discharge in anticipation of limb and trunk movements, whereas caudate neurons fire prior to eye movements. Anticipatory discharge is part of a movement selection process – it can precede the initiation of movement by several seconds. Discharges of some striatal neurons vary according to the location in space of the destination of a movement, rather than with the starting position of the limb relative to the destination. Thus, the activity of these cells may encode the decision to move toward a Figure 18.2 goal rather than the direction and amplitude of the actual movement necessary to reach the goal.  Circuits of the basal ganglia Neurons of the internal segment of globus pallidus (iGB) are tonically (spontaneously) active and inhibit VA/VL complex of thalamus. To initiate movement those neurons have to be inhibited. Medium spiny neurons in putamen inhibit iGB enabling movement initiation while input from subthalamic nucleus has excitatory input and thus strengthens their inhibitory effect on thalamus supressing movement. Substantia nigra pars reticulata serves analogous function to globus pallidus, but for oculomotor loop globus pallidus ~ substantia nigra pars reticulata Figure 18.4  Circuits of the basal ganglia Neurons of the internal segment of globus pallidus (iGB) are tonically (spontaneously) active and inhibit VA/VL complex of thalamus. To initiate movement those neurons have to be inhibited. Medium spiny neurons in putamen inhibit iGB enabling movement initiation while input from subthalamic nucleus has excitatory input and thus strengthens their inhibitory effect on thalamus supressing movement. Substantia nigra pars reticulata serves analogous function to globus pallidus, but for oculomotor loop globus pallidus ~ substantia nigra pars reticulata Figure 18.4  Output loops of the basal ganglia: disinhibitory circuit – direct pathway (Striatum) Figure 18.5 Figure nomenclature: Tonic – background activity when there are no external inputs Transient – effect when stimulus is received Output loops of the basal ganglia: direct and indirect pathways (Striatum) Figure 18.7 Centre-surround functional organisation The task of direct-indirect pathway circuits is to facilitate the selection of a motor program, facilitate the initiation of volitional movement and suppress competing motor programs. The focused selection is achieved by antagonistic interaction between direct and indirect pathways in a centre-surround fashion. On average, more than 100 medium spiny neurons in putamen innervate each cell in the globus pallidus. As part of the direct pathway individual axons from the corpus striatum to the internal segment of the globus pallidus tend to form synapses within localised limited area. In contrast, afferents from the subthalamic nucleus representing indirect pathway are distributed much more evenly throughout the internal segment, providing means for the indirect pathway to suppress competing motor programs in a broader "surrounding" set of functional units. Figure 18.8  Modulatory effect of dopamine Substantia nigra compacta Axons from substantia nigra compacta form dopaminergic synapses on the medium spiny neurons. The same nigral neurons can provide excitatory inputs to the medium spiny neurons that project to the internal globus pallidus (the direct pathway) and inhibitory inputs to the medium spiny neurons that project to the external globus pallidus (the indirect pathway). Those antagonistic effects are determined by expression of two different types of dopamine receptors on functionally different medium spiny neurons. Medium spiny neurons that belong to the direct pathway express D1 receptor which has an excitatory effect, while medium spiny neurons that belong to the indirect pathway express D2 receptor which causes inhibition of activity. This dopaminergic input to the corpus striatum may contribute to reward- related modulation of behaviour. For example, in monkeys, the latencies of saccades toward a target are shorter when the goal of the movement is associated with a larger reward. Parkinson's disease (hypokinetic) (Striatum) Patient examination videos – refer to practical class #4  Parkinson's disease (hypokinetic) Resources for extended study (optional): what causes tremor in Parkinson’s disease ABSTRACT: Tremor in Parkinson's disease has several mysterious features. Clinically, tremor is seen in only three out of four patients with Parkinson's disease, and tremor-dominant patients generally follow a more benign disease course than non-tremor patients. Pathophysiologically, tremor is linked to altered activity in not one, but two distinct circuits: the basal ganglia, which are primarily affected by dopamine depletion in Parkinson's disease, and the cerebello-thalamo-cortical circuit, which is also involved in many other tremors. The purpose of this review is to integrate these clinical and pathophysiological features of tremor in Parkinson's disease. We first describe clinical and pathological differences between tremor- dominant and non-tremor Parkinson's disease subtypes, and then summarize recent studies on the pathophysiology of tremor. We also discuss a newly proposed 'dimmer-switch model' that explains tremor as resulting from the combined actions of two circuits: the basal ganglia that trigger tremor episodes and the cerebello-thalamo-cortical circuit that produces the tremor. Finally, we address several important open questions: why resting tremor stops during voluntary movements, why it has a variable response to dopaminergic treatment, why it indicates a benign Parkinson's disease subtype and why its expression decreases with disease progression.  Huntington's disease (hyperkinetic) (Striatum) In Huntington's disease subgroup of medium spiny neurons that belong to the indirect pathway (project to the external segment of the globus pallidus) degenerate and thus remove suppression of unwanted movements. Patient examination videos – refer to practical class #5 At rest when there are no external inputs Striatum iGP VA/VL M. Cortex eGP Subthalamic n.  Active - direct pathway (initiation of desired movement) Striatum iGP VA/VL Active - indirect pathway (suppression of unwanted movements) Striatum iGP VA/VL eGP Subthalamic n. While the desired movement is being sustained, unwanted movements are supressed.