TASK 2 – BASAL GANGLIA LEARNING GOALS
Tonic inhibition – constantly happening, always in motion
Transient inhibition – happens in bursts, based on stimulation / activation
Cortex à striatum = transient
LEARNING GOAL 2.1: THE DIRECT PATH: DOUBLE INHIBITION.
DISCUSS THE ORGANIZATION OF THE DIRECT PATH OF THE BASAL GANGLIA (FROM
CORTEX BACK TO CORTEX)
INPUT
• The caudate & putamen (corpus striatum) comprise the input zone of the basal ganglia, meaning that
axons from the cerebral cortex and substantia nigra neurons first reach the basal ganglia here.
o Medium spiny neurons- a class of cells in the striatum, whose dendrites are the
destinations of the incoming axons from the cerebral cortex.
§ Their large dendritic trees allow them to integrate inputs from a variety of cortical,
thalamic and brainstem structures.
• Axons of the medium spiny neurons converge on neurons in the pallidum (including the globus
pallidus and the substantia nigra pars reticulata), which are the main basal ganglia outputs.
• The striatum receives input from all cortical areas, except for the primary visual & primary auditory
cortices.
o The heaviest projections are from association areas in the frontal & parietal lobes, but there
are also significant contributions from the temporal, insular, and cingulate cortices.
o All of these projections are referred to as the corticostriatal pathway.
• Axons of corticocortical, corticothalamic and corticospinal pathways all form excitatory
glutamatergic synapses on the dendritic spines of medium spiny neurons.
o The number of spiny neurons contacted by a single axon is extremely large.
o The divergence of input from corticostriatal axons allows a single medium spiny neuron to
integrate the influences of thousands of cortical cells.
OUTPUT
,• The medium spiny neurons of the striatum have inhibitory GABAergic projections to the globus
pallidus and substantia nigra pars reticulata (SNPR).
o The globus pallidus and SNPR perform comparable functions; the SNPR may be
understood as a part of the globus pallidus that was displaced to the midbrain by the
formation of the internal capsule & cerebral peduncle.
o The striatal projections to these 2 nuclei resemble the corticostriatal pathways, because
they terminate in rostrocaudal bands, whose locations vary with the locations of the
sources in the striatum.
• On average, more than 100 medium spiny neurons innervate each cell in the globus pallidus.
o However, axons from the striatum sparsely contact many pallidal neurons before
terminating densely on the dendrites of a particular neuron.
o Consequently, many medium spiny neurons exert a broad but functionally weak influences
over many pallidal neurons, while at the same time influencing strongly a subset of neurons
in the globus pallidus or SNPR.
o This pattern of innervation is important for the striatum's role in the selection & initiation of
intended motor programs.
• The efferent neurons of the globus pallidus and SNPR together give rise to the major pathways that
allow the basal ganglia to influence motor activity at the level of motor cortex & brainstem.
o The cortical pathway arises primarily in the internal segment (medial division of globus
pallidus), and reaches the motor cortex via a relay in the ventral anterior and ventral lateral
nuclei of the dorsal thalamus.
o These thalamic nuclei project to motor cortical areas, completing a loop that originates in
multiple cortical areas and terminates in the motor areas of the frontal lobe, after
processing from the basal ganglia & thalamus.
o Many efferent axons from SNPR synapse on neurons in the superior colliculus that
command head & eye movements, without a thalamic relay.
! This difference between the globus pallidus & SNPR is not absolute because many SNPR axons
also project to the thalamus, where they contact relay neurons that project to the frontal eye
fields of the premotor cortex
• Because the medium spiny neurons of the striatum also are
GABAergic and inhibitory, the net effect of the excitatory inputs that
reach the striatum from the cortex is to inhibit the tonically active
inhibitory cells of the globes pallidus and substantia nigra pars
reticulata
o Ex: When pallidal cells are inhibited by activity of the medium
spiny neurons = the thalamic neurons are disinhibited and
can relay signals from other sources to the upper motor
neurons in the cortex
o This disinhibition allows the upper motor neurons to send
commands to local circuit and lower motor neurons that initiate movement
• High levels of output = prevention of unwanted movement by tonically inhibiting thalamus & colliculi
• Thus, when cortex active, those nuclei become disinhibited and can command to initiate movement
, DIRECT • Projections from medium spiny neurons à striatum à internal segment of globus
pathway pallidus
• Release from tonic inhibition the thalamic neurons that drive upper motor neurons
• Initiation of movement
• When cortex active à inhibited internal segment à excited thalamus à GO
• When activated releases thalamocortical and collicular circuits from tonic inhibition
o Transiently inhibitory projections from the caudate and putamen project to
tonically active inhibitory neurons in the internal segment of the globus
pallidus
o Which project in turn to the VA/VL complex of the thalamus
o Transiently excitatory input to the caudate and putamen from the cortex and
substantia nigra are also shown, as is the transiently excitatory input from
the thalamus back to the cortex
INDICATE THE CONNECTIONS AND THE NEUROTRANSMITTERS USED IN EACH
CONNECTION. EXPLAIN THE PRINCIPLE OF DOUBLE INHIBITION
• When striatum receives excitatory input from the cortex, the striatum suppresses the activity of the
second inhibitory neuron (globus pallidus) via inhibitory signals (GABA (If Striatum excited = always
release of GABA because neurons are GABAergic)
• The result of this is a reduction of the inhibitory influence (less GABA) that the globus pallidus
has over the thalamus, so-called disinhibition of the thalamus, which is equivalent to the excitation
of the motor cortex.
• So the final function of the direct pathway of the basal ganglia is to excite the motor cortex or to
increase the motor activity.
• 2 successive inhibitory links is the most efficient way to make a selected pattern stand out from
the background
o The double inhibition of the direct pathway is relatively unique to the BG. Particularly useful
for selecting a response in a competitive system
Tonic inhibition – constantly happening, always in motion
Transient inhibition – happens in bursts, based on stimulation / activation
Cortex à striatum = transient
LEARNING GOAL 2.1: THE DIRECT PATH: DOUBLE INHIBITION.
DISCUSS THE ORGANIZATION OF THE DIRECT PATH OF THE BASAL GANGLIA (FROM
CORTEX BACK TO CORTEX)
INPUT
• The caudate & putamen (corpus striatum) comprise the input zone of the basal ganglia, meaning that
axons from the cerebral cortex and substantia nigra neurons first reach the basal ganglia here.
o Medium spiny neurons- a class of cells in the striatum, whose dendrites are the
destinations of the incoming axons from the cerebral cortex.
§ Their large dendritic trees allow them to integrate inputs from a variety of cortical,
thalamic and brainstem structures.
• Axons of the medium spiny neurons converge on neurons in the pallidum (including the globus
pallidus and the substantia nigra pars reticulata), which are the main basal ganglia outputs.
• The striatum receives input from all cortical areas, except for the primary visual & primary auditory
cortices.
o The heaviest projections are from association areas in the frontal & parietal lobes, but there
are also significant contributions from the temporal, insular, and cingulate cortices.
o All of these projections are referred to as the corticostriatal pathway.
• Axons of corticocortical, corticothalamic and corticospinal pathways all form excitatory
glutamatergic synapses on the dendritic spines of medium spiny neurons.
o The number of spiny neurons contacted by a single axon is extremely large.
o The divergence of input from corticostriatal axons allows a single medium spiny neuron to
integrate the influences of thousands of cortical cells.
OUTPUT
,• The medium spiny neurons of the striatum have inhibitory GABAergic projections to the globus
pallidus and substantia nigra pars reticulata (SNPR).
o The globus pallidus and SNPR perform comparable functions; the SNPR may be
understood as a part of the globus pallidus that was displaced to the midbrain by the
formation of the internal capsule & cerebral peduncle.
o The striatal projections to these 2 nuclei resemble the corticostriatal pathways, because
they terminate in rostrocaudal bands, whose locations vary with the locations of the
sources in the striatum.
• On average, more than 100 medium spiny neurons innervate each cell in the globus pallidus.
o However, axons from the striatum sparsely contact many pallidal neurons before
terminating densely on the dendrites of a particular neuron.
o Consequently, many medium spiny neurons exert a broad but functionally weak influences
over many pallidal neurons, while at the same time influencing strongly a subset of neurons
in the globus pallidus or SNPR.
o This pattern of innervation is important for the striatum's role in the selection & initiation of
intended motor programs.
• The efferent neurons of the globus pallidus and SNPR together give rise to the major pathways that
allow the basal ganglia to influence motor activity at the level of motor cortex & brainstem.
o The cortical pathway arises primarily in the internal segment (medial division of globus
pallidus), and reaches the motor cortex via a relay in the ventral anterior and ventral lateral
nuclei of the dorsal thalamus.
o These thalamic nuclei project to motor cortical areas, completing a loop that originates in
multiple cortical areas and terminates in the motor areas of the frontal lobe, after
processing from the basal ganglia & thalamus.
o Many efferent axons from SNPR synapse on neurons in the superior colliculus that
command head & eye movements, without a thalamic relay.
! This difference between the globus pallidus & SNPR is not absolute because many SNPR axons
also project to the thalamus, where they contact relay neurons that project to the frontal eye
fields of the premotor cortex
• Because the medium spiny neurons of the striatum also are
GABAergic and inhibitory, the net effect of the excitatory inputs that
reach the striatum from the cortex is to inhibit the tonically active
inhibitory cells of the globes pallidus and substantia nigra pars
reticulata
o Ex: When pallidal cells are inhibited by activity of the medium
spiny neurons = the thalamic neurons are disinhibited and
can relay signals from other sources to the upper motor
neurons in the cortex
o This disinhibition allows the upper motor neurons to send
commands to local circuit and lower motor neurons that initiate movement
• High levels of output = prevention of unwanted movement by tonically inhibiting thalamus & colliculi
• Thus, when cortex active, those nuclei become disinhibited and can command to initiate movement
, DIRECT • Projections from medium spiny neurons à striatum à internal segment of globus
pathway pallidus
• Release from tonic inhibition the thalamic neurons that drive upper motor neurons
• Initiation of movement
• When cortex active à inhibited internal segment à excited thalamus à GO
• When activated releases thalamocortical and collicular circuits from tonic inhibition
o Transiently inhibitory projections from the caudate and putamen project to
tonically active inhibitory neurons in the internal segment of the globus
pallidus
o Which project in turn to the VA/VL complex of the thalamus
o Transiently excitatory input to the caudate and putamen from the cortex and
substantia nigra are also shown, as is the transiently excitatory input from
the thalamus back to the cortex
INDICATE THE CONNECTIONS AND THE NEUROTRANSMITTERS USED IN EACH
CONNECTION. EXPLAIN THE PRINCIPLE OF DOUBLE INHIBITION
• When striatum receives excitatory input from the cortex, the striatum suppresses the activity of the
second inhibitory neuron (globus pallidus) via inhibitory signals (GABA (If Striatum excited = always
release of GABA because neurons are GABAergic)
• The result of this is a reduction of the inhibitory influence (less GABA) that the globus pallidus
has over the thalamus, so-called disinhibition of the thalamus, which is equivalent to the excitation
of the motor cortex.
• So the final function of the direct pathway of the basal ganglia is to excite the motor cortex or to
increase the motor activity.
• 2 successive inhibitory links is the most efficient way to make a selected pattern stand out from
the background
o The double inhibition of the direct pathway is relatively unique to the BG. Particularly useful
for selecting a response in a competitive system
