organization of the basal ganglia

the basal ganglia are large structures that are easily identified in structural MRI scans

the basal ganglia have three input nuclei that receive projections from all parts of cerebral cortex

Among these three input nuclei, the caudate processes cognitive information, the putamen processes sensorimotor information, and the nucleus accumbens processes limbic information.

the caudate and putamen are cytologically identical and have similar embryological origins

The caudate, putamen, and nucleus accumbens have identical cell types and perform similar computations, but receive inputs from different cortical regions. In primates, the separation between caudate and putamen is due to fibers growing between the cortex and thalamus during embryological development. These nuclei are not separated in rats.

the mid-level basal ganglia looks like this

includes:

• caudate

• ventroanterior thalamus

• globus pallidus

• putamen

• amygdala

the caudal level of the basal ganglia look like this

includes:

• caudate

• ventrolateral thalamus

• ventroanterior thalamus

• globus pallidus

• putamen

• subthalamic nucleus

basal ganglia loops are topographically segregates to process different types of information

the basal ganglia-thalamocortical (BG-TC) loops are comprised of several different functional channels

• Parallel channels or loops

• Processes related cortical information

• Corticostriatal convergence from related cortical areas

• Terminate in specific frontal lobe areas

• Four loops identified

  • sensorimotor (SI, SII, motor areas)

  • oculomotor (frontal eye fields)

  • orbitalfrontal (limbic / emotions / drives)

  • prefrontal (cognitive thoughts)

in monkeys, the putamen receives convergent inputs from the primary motor (MI) and somatosensory (SI) cortices

• 35S-methionine autoradiography (anterograde tracing)

• Injections of anterograde tracers into MI or SI cortex revealed bilateral labeling in overlapping parts of the dorsal lateral putamen

rat SI barrel cortex projects to the dorsolateral striatum (DLS)

in rats, the dorsolateral receives convergent inputs from the primary motor (MI) and somatosensory (SI) cortices

the putamen (in humans) or dorsolateral striatum (in rats) is needed for the expression of sensorimotor habits

• Defining characteristics of sensorimotor habits

  • well learned, highly repetitive behaviors

  • stereotyped sequences of motor activity

  • behaviors frequently evoked in familiar contexts

  • resemble a stimulus-response (S-R) association

  • executed automatically (almost non-consciously)

  • insensitive to reward devaluation

the dorsolateral striatum (DLS) in the rat homologue of the primate putamen; it mediates repetitive sensorimotor behaviors

• Grooming

  • DLS neurons encode stereotyped grooming sequences

  • grooming sequences are blocked by DLS lesions

• Exploratory Whisking

• DLS neurons discharge rhythmically during whisking

• whisker contacts with stimuli evoke stereotyped responses

• resembles S-R associations

in parkinson’s disease, postmortem analysis indicates that dopamine loss is greatest in the putamen

non-invasive imaging indicates that dopamine loss initially appears in the putamen of PD patients

the basal ganglia enable selection of specific behavioral and cognitive programs while suppressing competing programs

• Many insights about the function of the basal ganglia have come from analysis of damage to the system and the ensuing behavioral symptoms

• Ballism

  • uncontrollable ballistic movements

• Parkinson’s Disease

  • poverty of movement

  • difficulty initiating movement

• Athetosis and Chorea

  • involuntary movements

the basal ganglia contain multisynaptic pathways that proceed from cortex to the thalamus

cortical processing of information from the basal ganglia and the cerebellum depends on inputs from the thalamus (part 1)

Thalamic nuclei concerned with transmitting information to motor cortex are located in the rostral part of the ventral tier, namely the ventral lateral and the ventral anterior nuclei.

cortical processing of information from the basal ganglia and the cerebellum depends on inputs from the thalamus (part 2)

the basal ganglia receive three main types of inputs

• Corticostriatal (caudate & putamen)

  • glutamate inputs from many cortical regions

• Nigrostriatal

  • dopamine inputs from substantia nigra pars compacta

• Thalamostriatal

  • parafasiculus

  • centromedian

what are the differential roles of corticostriatal and thalamostriatal inputs?

• Internally-generated signals

  • Prefrontal cortex sends the striatum intention commands

  • MI and SI cortex send sensorimotor context signals that accompany voluntary behavior

• Externally-generated sensory signals

  • Sensory inputs that require re-direction of attention and possible selection of a new behavior in response to unexpected stimuli (centromedian and parafascicular nuclei)

  • Sensory inputs involved in the formation and maintenance of S-R associations that mediate well-learned sensorimotor habits (POm)

medium spiny neurons represent the main computational unit in the striatum and accumbens

• Medium spiny neurons comprise > 90% of all striatal neurons and perform most of its integrative functions.

• Their soma have medium diameters (~20 mm) and their dendrites are covered with spines, which are specialized for integrating synaptic inputs.

• Medium spiny neurons provide the only source of output from the striatum; all other striatal neurons are local interneurons.

• Medium spiny neurons use the inhibitory transmitter, GABA, co-localized with a neuropeptide.

dopamine modulates the impact of corticostriatal inputs

• Excitatory glutamatergic projections from the cortex terminate on the spine heads of medium spiny neurons.

• Dopaminergic projections from the substantia nigra terminate on the spine necks or on more proximal parts of the dendritic shaft.

• Dopamine synapses are in a location where they modulate or “gate” the effectiveness of corticostriatal excitation.

synaptic sites suggest that dopamine modulates corticostriatal interactions

Thalamostriatal synapses tend to be located on proximal dendrites. This position is less likely to be modulated by dopaminergic inputs, which are located more distally on the necks of dendritic spines.

the basal ganglia contain two parallel pathways: direct and indirect

Striatal Projections

• Direct Pathway to Output Nuclei

  • int. globus pallidus

  • substantia nigra pars reticulata

  • GABA, substance P, dynorphin

• Indirect Pathway

  • ext. globus pallidus

  • GABA, enkephalin

the basal ganglia contain some internuclear connections

Internuclear Connections

• Subthalamic Fasciculus

  • GPext to subthalamic nuc.

  • Subthalamic nuc. to GPext

  • Subthalamic nuc. to GPint/SNpr

• Dopaminergic Pathways

  • SNpc to striatum

  • Ventral tegmental area to Nuc. Acc.

basal ganglia outputs terminate in the thalamus

Tracer injections into the medial pallidal segment indicate that this output nucleus projects to the ventroanterior and ventrolateral nuclei in the thalamus.

basal ganglia outputs take several routes to the thalamus

• Internal Globus Pallidus

  • to motor thalamus (VA, VLo)

  • via lenticular fasciculus

  • via ansa lenticularis

• Substantia Nigra pars reticulata

  • to motor thalamus (VA)

  • medial dorsal thalamus

  • pedunculopontine, sup. coll.

the best (but not perfect) model of the basal ganglia is the one proposed by mahlon delong

• Output nuclei (GPi/SNpr) are tonically active & inhibit thalamus (VA/VL)

• Opposing influences on GPi/SNpr

  • Direct pathway (accelerator)

  • Indirect Pathway (brake)

• Dopamine has opposite effects on direct and indirect pathways

• Disinhibition plays a key role

excessive activation of the direct pathway produces hyperkinetic disorders

• Direct Pathway activation:

  • Increased inhibition of GPi and SNpr

  • Motor thalamus released from inhibition

• Consistent with clinical conditions:

  • Hemiballism (flailing movements - contra limbs)

  • produced by subthalamic lesions

• Huntington’s Chorea:

  • loss of neostriatal neurons

  • enkephalin colocalized with GABA

huntington’s chorea is a hyperkinetic disorder

• Images of the brain from a patient with Huntington’s disease reveals enlarged ventricles and shrunken caudate and putamen nuclei bilaterally.

• According to the DeLong model, neuronal loss in the caudate is due primarily to the loss of neurons that use enkephalin co-localized with GABA.

excessive activation of the indirect pathway produces hypokinetic disorders

• Indirect Pathway activation

  • Increased inhibition of GPe

  • Subthalamic activity increases

  • Thalamus is inhibited by GPi/SNpr

  • Reduced thalamocortical activation of motor/premotor cortex

• Consistent with clinical conditions

  • Parkinson’s Disease (loss of dopamine results in loss of inhibition of indirect pathway)

  • Experimental MPTP treatment

parkinson’s disease is a hypokinetic disorder

• Akinesia

  • poverty of movement

  • difficulty initiating movement

• Bradykinesia

  • slow, shuffling gait

• Masked facial expression

  • unblinking (reptilian) stare

• Paralysis agitans

  • tremor at rest (4-6 Hz)

• Chronic, progressive degeneration

the anatomy of the basal ganglia has prompted several strategies for treating parkinson’s disease

• Transplants

  • fetal tissue (substantia nigra)

  • dopamine cells in adult kidney (adrenal medulla)

• Surgical Ablation

  • ventral globus pallidus

  • VA, VL thalamus (tremor)

• Microelectrode Stimulation

  • subthalamic stimulation

what is a potential problem with pallidotomy?

A potential problem with a ventral pallidotomy is that the optimal site for the lesion is located close to the optic tract and it may produce homonymous hemianopsia.

chronically implanted electrodes targeting the STN to treat Parkinson’s disease will also stimulate the zona incerta