Anatomy of the Basal Ganglia The striatum (caudaute/putamen) and subthalamic nucleus (STN) receive excitatory input from

the cerebral cortex. Dopamine-releasing neurons in the substantia nigra pars compacta (SNpc) connect to neurons in the striatum and modulate the inputs from the cortex. There is an inhibitory connection from the striatum to the globus pallidus internal segment (GPi) and the substantia nigra pars reticulara (SNpr), as well as an excitatory projection from STN to GPi that is divergent (one STN neuron contacts many Gpi neurons). This pathway is called the direct pathway. Another, indirect pathway of inhibitory connections extends from the striatum to the globus pallidus external segment (Gpe) to the STN to the GPi. The GPi and SNpr send inhibitory output via collaterals to the thalamus and brain stem. The SNpr is involved in eye movements. Types of Neurons in the Striatum Medium spiny neuronsmake up 95% of the total. Use GABA as a transmitter. Are the output neurons of the striatum. Large aspiny neuronsinterneurons that use ACh as a transmitter. Medium aspiny cellsinterneurons that use somatostatin as a neurotransmitter. Small aspiny cellsinterneurons that use GABA. Neuron Firing in the Basal Ganglia Neurons in the putamen and throughout the basal ganglia fire after those in the motor cortex, implying that the striatum is not involved primarily in the initiation of movement. The firing of SNpc neurons increases in response to behaviorally significant events such as reward or the presentation of instructional cues. These neurons can also learn to respond to a cue that predicts a reward. Consequences of Damage to the Basal Ganglia Inactivating the putamen leads to slowed movement of the contralateral limb. Huntingtons Disease, which causes involuntary movements, is linked to the death of neurons that project from the putamen to the GPe. Damage to the STN causes large involuntary movements of the limbs. Lesions to the GPi cause slowness of movement, linked to a tendency of the limbs to assume an abnormally flexed posturethat is, an inability to turn off muscle activity. Damage to the SNpc causes symptoms of Parkinsons diseasetremor and slowed movement.

Model of Basal Ganglia Function One hypothesis suggests that the basal ganglia automatically execute learned movement sequences. This theory is supported by the fact that patients with PD have difficulty coordinating complex movements of several body parts in sequence, such as when writing. Another suggests that the basal ganglia form two opposing motor pathways, the direct and indirect pathways described above. Increased activity in the direct pathway causes excessive movement, while activity in the indirect pathway inhibits movement. A third suggests that the basal ganglia act as a brake on motor movement. The theory suggests that STN neurons excite the GPi widely, inhibiting motor output. At the same time, signals sent from the cortex to the striatum to the GPi inhibit a small part of the GPi, selecting a certain motor pattern to be disinhibited and suppressing surrounding patterns. Anatomy of the Cerebellum The cerebellar cortex is divided into three lobes: anterior, posterior, and flocculonodular. Each lobe consists of thin folds called folia. This sheet is laid over four cerebellar nuclei (CN) on each side. Three cerebellar peduncles on each side connect the cerebellum to the brain stem. The cortex consists of three layers. The granular cell layer, on the bottom, contains an enormous number of granule cells. The Purkinje cell layer contains cell bodies of PCs, and the molecular layer contains only dendrites and axons. Incoming information from all over the brain sends information via mossy fibers (MFs) to the granule cells. These cells relay the information to the molecular layer via parallel fibers (PFs), which make contact with the dendrites of PCs. In addition, error correction signals are sent from the inferior olive to PCs via climbing fibers (CFs). Each PC is only contacted by one CF. The PCs send inhibitory signals to the CN. These nuclei are linked reciprocally to populations of neurons in other parts of the brain, forming attractor networks. Long-term Depression (LTD) Takes Place Between the Synapses of PFs and PCs Unlike LTP, LTD requires the presence of three factors in order to take place: 1) Depolarization of the dendrite 2) Activation of glutamate receptors on a particular spine on the dendrite 3) The firing of a CF (training signal) hundreds of milliseconds later This process marks synapses causing movements that result in error and causes them to be less effective. Plasticity in the cerebellum is thought to be involved only in adjusting motor responses, not in forming a link between a conditioned and unconditioned stimulus.