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Globus Pallidus

From: Neuropsychiatry, Neuropsychology, Clinical Neuroscience
by Rhawn Joseph, Ph.D.
(Academic Press, New York, 2000)

Globus Pallidus


By Rhawn Joseph, Ph.D.

Structural Overview

The basal ganglia is composed of several major nuclei which include the corpus (or dorsal) striatum ("striped bodies") i.e., the caudate and putamen which are extensively interconnected and which project to a variety of brain areas including the immediately adjacent globus pallidus ("pale globe"). The dorsal globus pallidus although related to the hypothalamus and midbrain, is in many respects coextensive and appears to merge with the putamen giving the entire structure the appearance of a camera lens. Hence the globus pallidus and the putamen are referred to as the lenticular nucleus ("lens"). [-INSERT FIGURES 2 & 3 ABOUT HERE-]

The inferior ventral globus pallidus (also referred to as the ventral pallidum or substantia innominata) is also part of the limbic (ventral) striatum and in fact eventually merges with the centro-medial amygdala and receives extensive projections from the lateral amygdala, the olfactory tubercle, and nucleus accumbens.

The amydalostriatal gray consisted of both dorsal and ventral components, and so too does the human striatum--also referred to as the limbic (ventral) striatum. The substantia innominata, nucleus accumbens, olfactory tubercle constitute the limbic striatum.


The "basal ganglia" (striatum, subthalamic nucleus) receives much of its input from the neocortex (Jones & Powell, 1970; Pandya & Vignolo, 1971), and the amygdala, and to a mimimal extent the hippocampus. The majority of these incoming fibers are excitatory and terminate in the corpus striatum and subthalamic nucleus. Specifically, the anterior portion of the frontal lobes projects to the head of the caudate whereas the more posterior putamen receives converging and overlapping input from the primary and secondary motor and somesthetic cortices (Jones & Powell, 1970; Pandya & Vignolo, 1971). This structure does not receive any direct input from the peripheral sensory or motor systems.


The main avenue of output is via the globus pallidus (and in the brainstem, the substantia nigra) which projects to the thalamus and the brainstem via the "extra-pyramidal system". The basal ganglia does not project directly to the spinal cord. The majority of these outgoing axons arise from "spiny" neurons, and these are responsible for transmitting striatal impulses to the globus pallidus (GP). These are predominantly inhibitory and employ GABA (and various peptides, e.g. substance P) as neurotransmitters.


The GP transmits to the brainstem and to the motor thalamus and subthalamic nucleus (Mink & Thach, 1991; Parent & Hazrati 1995). The motor thalamus in turn projects to the frontal motor areas i.e. the primary, secondary, supplementary motor areas and frontal eye fields, including the anterior frontal lobe.


The subthalamic nucleus, is directly linked with the hypothalamus and midbrain, and receives excitatory input from all frontal motor areas; Unlike the globus pallidus, output from the subthalamic nucleus is excitatory, and it in fact projects back to the globus pallidus.

The GP, therefore, receives diffuse exitatory input from the subthalamic nucleus, and converging inhibitory input from the striatum, and the transmits the bulk of its inhibitory impulses to the motor thalamus which acts on the frontal neocortical motor areas. Thus a complex feedback loop involving inhibitory and excitatory circuits is maintained in this area--feedback which presumably assists in the guidance of movements directly controlled by the frontal motor areas, as well as those initiated internally vs externally (Schultz & Romo, 1992).

Conversely, disturbances in this feedback loop, or in the neurotransmitters which maintain it, can result in a host of motor disturbances, ranging from the rigidity of Parkinson's disease and catatonia to chorea, hemiballismus, or "restless leg syndrome." Restless leg syndrome, for example, is a chronic condition which presumably afflicts about 5% of the population, and is characterized by a constant, sometimes painful urge to move the limbs which is only relieved by walking (e.g. Tergau, et al., 1999; Turjanski, et al., 1999). Functional imaging indicates that this disorder is directly related to disturbances in striatal dopamine binding and uptake, particularly in the caudate and putamen (Turjanski, et al., 1999). Presumably, this disturbances is thus a function of abnormal activity in these structures which begin to fire in the absence of any desire to move, thus inducing an urge to move, coupled with excessive activity in the frontal motor areas (e.g., Tergau, et al., 1999)

In this regard it is noteworthy that neurons in the striatum begin firing prior to movement, 20 ms on average. They increase their rate of firing at the start of specific movements, and cease to fire following movement (Montgomery & Bucholz, 1991; Schultz & Romo, 1992). Moreover, neurons related to movement are somatotopically organized such that those that represent the leg, face or arm, cluster together within the striatum, and increase their activity prior to and during movements of the leg, face or arm, etc.,


The corpus striatum, GP, and subthalamic nucleus, however, represent only the dorsal aspect of the "basal ganglia." Ventral to and intimately associated with the dorsal striatum is the limbic striatum, portions of which have also been referred to as the "extended amygdala." Indeed, the amygdala is a major component of the "basal ganglia," and these structures function as a cohesive interacting unit for the purposes of defensive and other affective behaviors regarding gross body movements, such as kicking, flailing, running, and kicking.

The substantia innominata (ventral globus pallidus/nucleus basalis) merges with the centro-medial amygdala and receives extension projections from the lateral amygdala. Nevertheless, they do not completely separate, and the medial amygdala remains extensively interconnected with the limbic (ventral) striatum.


Catatonia, Parkinson's Disease, & Psychosis.

Lesions to the corpus striatum and lenticular nucleus (putamen and globus pallidus) can attenuate one's capacity to motorically express their emotions via the musculature; e.g. the face may become frozen and mask-like. These latter motor disturbances are well known symptoms associated with Parkinson's disease, a disturbance directly linked to dopamine deficiency (Fahn, 1999) and neuronal degeneration not only in the putamen (Goto, et al. 1990; Kish, et al. 1988; see also Hauser et al., 1999), but within the limbic striatum, i.e. the nucleus accumbens (see Rolls & Williams, 1987), as well as in the supplementary motor areas and medial frontal lobe -which maintains rich interconnections with the striatum.

However, when chemical or structural lesions extend beyond the basal ganglia and come to include the medial frontal lobe, not only might an individual suffer motor rigidity, they may become catatonic and experience extreme difficulty responding to external or internally mediated impulses (Joseph, 1999a). Various aspects of this symptom complex also characterize those with Parkinson's disease (see below).

Other disturbances associated with striatal abnormalities include Huntington's chorea, ballismus, restless leg syndrome, sensory neglect and apathy, obsessive compulsive disorders, mania, depression, "schizophrenia" and related psychotic states (Aylward et al. 1994; Baxter et al. 1992; Caplan, et al. 1990; Castellanos et al. 1994; Chakos et al. 1994; Davis, 1958; Deicken et al. 1995; Ellison, 1994; Rauch et al. 1994; Richfield, et al. 1987; Turjanski, et al., 1999). Severe memory loss and social-emotional agnosia and an inability to recongize friends or loved ones is also characteristic of striatal abnormalities, particularly disturbances involving the limbic striatum.

Thus although the basal ganglia is often viewed and described as a major motor center (detailed below), the functional capacities and symptoms associated with this group of nuclei are quite diverse, and vary depending on the nuclei and chemical neurotransmitters involved as well as the laterality, location, and extent of any lesion.


The limbic striatum consists of the nucleus accumbens, olfactory tubericle, the extended (centro-medial) amygdala, as well as the ventral aspects of the caudate, putamen and globus pallidus (-substantia innomminata).

The nucleus accumbens is located immediately beneath the anterior portion of the caudate and from a microscopic level appears to be part of the ventral caudate (Olton et al. 1991; Zaborszky et al. 1991). However, it maintains extensive interconnections with the amygdala as well as the hippocampus via the fimbria-fornix fiber bundle (DeFrance et al. 1985), which implicates this nuclei in memory functioning and probably the learning of visual-spatial and perhaps social-affective relationships.

Similarly, the dorsal portion of the substantia innominata ("great unknown") merges (dorsally) with the ventral globus pallidus (and ventrally with the centro-medial amygdala), and maintains interconnections with the accumbens, hippocampus, lateral amygdala, and dorsal medial (DM) nucleus of the thalamus (Young et al. 1984; Zaborszky et al. 1991) -the DM being involved in regulating neocortical arousal and information reception as well as memory (see chapter 19).

Like the accumbens, the substantia innominata (SI) is also important in memory functioning and has been implicated as one of the principle sites (along with the nucleus basallis) for the initial development of Alzheimers disease (see Olton et al. 1991; Zaborszky et al. 1991, for review of related details).

The nuclei of the limbic striatum are also interconnected with the lateral and medial hypothalamus, brainstem reticular formation, and the frontal and inferior temporal lobes (Everitt & Robbins, 1992; Groenewegen, et al. 1991; Heimer & Alheid, 1991; Kelly, et al. 1982; Mogenson & Yang 1991; Olton et al. 1991; Parent & Hazrati 1995; Van Hoesen, et al. 1981; Zaborszky et al. 1991). The limbic striatum is able, therefore, to exert widespread effects on neocortical and subcortical structures.

As noted, the limbic striatum receives DA from the mesolimbic system as does the amygdala. The amygdala also sends axons that terminate in striatal neurons immediately adjacent to those innervated by mesolimbic DA neurons (Kelly et al. 1982; Yim & Mogenson, 1983, 1989). Thus, a complex interactional loop is formed between these nuclei, the integrity of which, in part is dependent on the mesolimbic DA system which can act on the amygdala, hippocampus and limbic striatum simultaneously so as to modulate striatal reception of amygdala (Maslowski-Cobuzzi & Napier, 1994) and hippocampal excitatory signals, and regulate the transmission of accumbens input into the SI. Alterations in mesolimbic DA activity, therefore, can significantly influence limbic striatal, amygdala and hippocampal activity as well as the motoric expression of limbic impulses.

For example, depletions in mesolimbic DA can disrupt motor and social-emotional memory functioning; a condition compounded by DA influences on acetylcholine (ACh) neurons, and the effects of striatal DA on the reception of hippocampal, amygala, and neocortical input.

Indeed, the limbic striatum (and limbic system) contain high densities of ACh neurons which are involved in memory as well as motor functioning (Olton et al. 1991; McGaugh et al. 1992; Zaborszky et al. 1991). In fact, of all striatal nuclei, densities of DA (and ACh) neurons are highest within the (SI) and nucleus accumbens (Meredith et al. 1989) which in turn greatly influences the SI (which is a major source of neocortical ACh), as does the amygdala (Yim & Mogenson 1983) and hippocampus; i.e. these signals converge on the SI.


Alzhiemer's disease is associated with a profound loss of memory and cognitive and intellectual functioning, including, at its later stages, an inability to recognize friends, loved one's or their own personal identity. Alzhiemer's disease is estimated to afflict approximately 10% of those over age 65, and 50% of those over 85.

In its later stages, Alzhiemer's disease is associated with profound loss of cerebral functional capacity, coupled with neural degeneration and a loss of neurons and the development of amyloid (senile) plaque and neurofibrillary tangles. Because structures such as the substantia innominata, amygdala, and entorhinal cortex have been injured (Morrison et al. 1990; Gomez-Isla, et al., 2000; Rapoport 1990) it is thought that the destruction of this tissue and adjacent tissue accounts for the loss of memory, and social-emotional, facial recognition, and related visual abnormalities, including visual agnosia (Giannakoulos, et al., 1999).

However, because there is no single factor that has been implicated, and due to the number of associated disturbances, it has been argued that Alzheimer's disease and associated cognitive and memory disturbances are due to a "global cortico-cortical disconnection" syndrome (see Morrison et al. 1990; Rapoport 1990). Nevertheless, for the purposes of this chapter, the striatal contribution to this disorder will be emphasized.


As detailed in chapter 15, the amygdala and hippocampus provide massive input to the limbic striatum as well as the dorsal medial nucleus of the thalamus (DM) , the frontal lobes and reticular activating system, as does the accumbens and SI (see Heimer & Alheid, 1991; Koob et al. 1991; Mogenson & Yang 1991; Zaborszky et al. 1991). As noted, these nuclei, including the overlying entorhinal cortex, play a significant role in memory and the gating of information destined for the neocortex and appear to be part of a massive neural network designed to control information processing and to establish memory related neural networks (see also chapter 14). Presumably the nucleus accumbens apparently acts to integrate hippocampal and amygdala input, which is then transmitted to the SI which is also the recipient of limbic impulses concerned with cognitive, memory, and motoric activities (see Mogenson & Yang 1991).

In part, it appears that the accumbens and SI play an inhibitory (filtering) role on information processing, and may exert inhibitory (and counterbalancing) influences on the the medial frontal lobes, the DM, and corpus striatum (see Mogenson & Yang 1991). The amygdala exerts similar influences on these nuclei (chapter 15) and is also able to inhibit the SI and accumbens.

However, the role of the limbic striatum in cognitive and memory related activity also includes the learning of reward-related and aversion processes, the facilitation of approach and withdrawal responses and the memorization of where a reward or aversive stimulus was previously received (Everitt et al. 1991; Kelsey & Arnold 1994). In this regard the nucleus accumbens and SI are dependent on the medial and lateral amgydala, especially in the learning of negative experiences (Kelsey & Arnold 1994).

As noted, the SI is the primary source of neocortical cholinergic innervation (Carpenter 1991) and appears to be concerned with integrating social-emotional and cognitive input with motor memories and then storing them perhaps within the SI as well as within the neocortex. Hence, if the SI is lesioned the cholinergic projection system is disrupted, and cognitive as well as social-emotional memory functioning is negatively impacted.

Since the SI merges with and becomes coextensive with the centromedial amygdala (Heimer & Alheid 1991),and is an amygdala derivative, not suprisingly, a significant loss of neurons, neurofibrillary changes and senile plaques have been found in the amygdala (and hippocampus, Rapoport 1990), as well as in the SI, in patients with Alzheimer's disease and those suffering from degenerative disorders and memory loss (Herzog & Kemper, 1980; Mann, 1992; Sarter & Markowitsch, 1985). Degeneration in the amygdala would also account for the social-emotional agnosia and prosopagnosia that is common in the advanced states of Alzhiemer's disease; i.e. failure to recognize or remember loved ones (chapter 13).


Neuronal loss has also been reported in the entorhinal and parahippocampal areas of the inferior temporal lobe (see Morrison et al. 1990; Rapoport 1990) within which is buried the hippocampus and amygdala. Specifically, in addition to senile plaques, neurofibrillary tangles, a 40% to 60% loss of neurons during the early stages of this disease have been found in layers 4 and 2 of the entorhinal cortex (Gomez-Isla, et al., 2000)--the gateway to the hippocampus. Destruction of this tissue and adjacent tissue would also result in memory, social-emotional, facial recognition, and related visual abnormalities, including visual agnosia, as recently demonstrated among those with Alzheimer's disease (Giannakoulos, et al., 1999).

Indeed, among those with Alzheimer's disease, widespread atrophy, amyloid plaques, tangles, and metabolic disturbances have been noted in a variety of cortical areas with relative preservation of the motor and primary receiving areas (Rapoport 1990). Based on these findings it has been argued that Alzheimer's disease and associated cognitive and memory disturbances are due to a "global cortico-cortical disconnection" syndrome (see Morrison et al. 1990; Rapoport 1990); i.e., a loss of neurons in and interconnections with association neocortex, which in part would account for the cognitive deterioration.

The initiation of this deteriorative process may well be in the SI, and it may be due to an olfactory borne infection due to viral or bacterial invasion. That is, these bacterial or viral agents may enter the olfactory system and invade those structures directly innervated by the olfactory nerves, i.e. the amygdala, entorhinal cortex, and SI (Joseph, 1998d). On the other hand, or perhaps related to this scenario, are findings suggesting a genetic foundation for this disorder, such that defects in at least four specific genes (located on chromosomes 1, 14, and 21) may be responsible (Levy-Lehad et al., 1995; Saunders et al., 1993).

Given the likelihood that the limbic striatum and olfactory-limbic structures may be selectively involved in the early stages of Alzheimers, and given the fact that the SI provides cholinergic input to the neocortex, then the subsequent and progressive loss of SI (and amygdala) neurons might result in a progressive deterioration and cell death within the neocortex such that otherwise healthy neurons are killed. That is, since the SI contains high concentrations of cholinergic neurons which in turn project to widespread areas throughout the neocortex (reviewed in Carpenter 1991), perhaps the initial cell loss within the SI (also referred to as the nucleus basalis), may trigger further cell death in healthy neurons (which project to or receive fibers from the affected cells) which essentially become "pruned" and drop out form disuse.



As noted, some studies have indicated that those with Parkinson's disease demonstrate the greatest amounts of DA depletion and related DA neuronal degeneration within the putamen. Hence, many authors have argued that Parkinson's symptoms are a consequence of damage to this nuclei (e.g. Goto et al.1990), which in turn can result in the production of unwanted movements such as tremor. Presumably, in these instances, the medial (internal) globus pallidus (which receives putamen input) ceases to inhibit irrelevant motor activity.

The putamen receives much of it's input from the caudate and in particular the SMA, the secondary and primary motor cortex, as well as areas 5 and 7 of the parietal lobe (Jones & Powell, 1970; Pandya & Vignolo, 1971). Presumably the putamen, in conjunction with the caudate, transmits this information to the medial and lateral GP which in turn projects to the motor thalamus, and brainstem. However, like the caudate, the putamen and GP also project back to the motor neocortex, thus creating a very elaborate feedback loop (see Mink & Thach, 1991; Parent & Hazrati 1995) whose origin may begin in the SMA (Alexander & Crutcher, 1990; Crutcher & Alexander, 1990) or perhaps the limbic system (chapter 13).

For example, when anticipating or preparing to make a movement, but prior to the actual movement, neuronal activity will first begin and then dramatically increase in the SMA, followed by activity in the secondary and then the primary motor area (see chapter 19), and then the caudate and last of all the putamen-GP (Alexander & Crutcher, 1990; see also Mink & Thach, 1991).

Ignoring for the moment the role of the limbic system, this indicates that impulses to move first appear in the SMA and that other motor regions are temporally-sequentially recruited in a step-wise fashion; i.e. SMA - premotor - primary motor - caudate - putamen - GP - motor thalamus/frontal motor areas - brainstem...

However, the caudate nucleus also contains neurons which become active prior to, and in anticipation of making body movements, and in response to associated auditory and visual environmental cues (Rolls, et al. 1983; Rolls & Williams, 1987). This caudate neuronal activity precedes, or occurs simultaneously with excitation in the lenticular nucleus, which also results (via feedback) in SMA activation. This is because the GP and the putamen not only receive caudate and neocortical afferents, but they project back to the frontal motor areas (as well as to the motor thalamus). Hence, parallel processing also occurs.


That is, activity in these regions quickly begins to overlap such that neurons in the motor neocortex and basal ganglia often remain activated simultaneously (Alexander & Crutcher, 1990). Moreover, the motor areas all independently send axons to the brainstem, with axons from different areas converging on the same motor neuron.

Therefore, activity in the motor areas is characterized by both temporal-sequential and parallel processing that in turn is made possible via feedback neural circuitry. Because these different networks are intimately linked and mutually interactive they make coordinated and goal directed movements possible.

Indeed, multiple feedback loops are probably also necessitated by the numerous variables and body- spatial- visual- kinesthetic- motor references, etc., that need to be computed in order to make a planned movement. Thus both temporal-sequential and parallel processing is necessitated as each area is functionally specialized to analyze specific types of information and to perform certain actions in semi-isolation as well performing other functions in parallel with yet other motor areas.


Just as different regions of the caudate appear to subserve different functions, a variety of neuronal types also characterize the lenticular nucleus. For example, preparatory and movement related neurons are segregated within the putamen (Alexander & Crutcher, 1990). This suggests that the putamen employs two different neural networks, one which executes movements, the other which prepares to make the movement; information which is normally transmitted to the GP as well as back to the motor neocortex.


The putamen appears to act at the behest of impulses arising in the neocortical motor areas (as well as the limbic system) and then only secondarily acts to prepare for and then to participate in the guidance of movement (Mink & Thach, 1991). In conjunction with the caudate, the putamen accomplishes this via signals transmitted to the medial and lateral GP, the motor thalamus, and brainstem reticular formation (Marsden & Obeso, 1994) and then back to the motor neocortex (see also Parent & Hazrati 1995, for a related review).

As noted, the putamen and globus pallidus are also coextensive (the lenticular nucleus) and in many respects function as a prepatory motor unit involved in the guidance, and perhaps even the learning of various motor activities (Crutcher & DeLong, 1984; Kimura, 1987). For example, alterations in neuronal activity have been demonstrated in the globus pallidus and the putamen during tasks involving learned body movement (Crutcher & DeLong, 1984). Lenticular neurons also become highly active when learned facial or limb movements are triggered in response to a particular auditory or visual stimulus associated with that movement (Kimura, 1987).

Some putamen and GP neurons also fire in response to reward but not to movement and vice versa (Kimura, et al. 1984). However, these same neurons do not respond when the same learned and rewarded movements are made spontaneously and in the absence of associated cues, or when they were no longer rewarded. These findings raise the possibility that specific neurons within these nuclei are responsive to motivational cues associated with movement and that these neurons utilizes these cues in preparation to make a movement (Kimura, 1987).


Neurons in the GP also selectively respond and change their activity when making ballistic movements, particularly those which are visually guided (Mink & Thach, 1991). However, activation occurs too late for these neurons to be involved in the initiation or planning of the movement (Mink & Thach, 1991). Conversely, destruction or massive inhibition of the GP can result in difficulty turning off a movement (see Mink & Thach, 1991) -thus giving each movement a ballistic quality. Similarly, destruction or massive inhibition of the GP can make it exceedingly difficulty to rapidly alternate between movements and thus switch from an ongoing to a different motor program (Hore & Vilis, 1980). This loss of control over motor programming with GP impairment extends even to attempts to make purposeful ballistic reaching or stepping movements (Horak & Anderson, 1984; Hore & Vilis, 1980), and the velocity and amplitude of these movements may in fact be significantly slowed and reduced (Mink & Thach, 1991).


The medial and lateral GP appear to play different and counterbalancing roles in the execution, inhibition and excitation of different motor programs (Crossman, et al. 1987; Marsden & Obeso, 1994). For example, the medial GP is believed to provide positive/excitatory feedback to the neocortical motor areas, whereas the lateral GP provides indirect "negative" and inhibitory feedback so that unwanted movements are prevented. Moreover, DA inhibits the medial GP, but excites the lateral GP (reviewed in Marsden & Obeso, 1994).

In consequence (at least in theory), reduced nigrostriatal DA levels can result in an overexcitation of the medial GP, which inhibits cortically mediated or initiated movements thereby producing akinesia (loss of movement), bradykinesia (reduction in movement) and hypokinesis (slowness of movement) coupled with tremor.

On the other hand excessive lateral GP (and limbic striatal) activity can also result in gross involuntary and excessive hyperkinetic and ballistic movements usually involving the limbs on the contralateral side of the body, along with choeriform movements and tremors. However, surgical destruction of the fibers tracts leading to and from the lateral and medial GP can significantly diminish such disturbances, including hemiballismus, tremor, dystonia, chorea and athetosis (see Carpenter & Sutin, 1983).

As noted above, lesions to the amygdala prior to the development of Parkinsonian and related symptoms, can also prevent the development of these motor abnormalities, which in part is due to the extensive interconnections maintained with these regions and the fact that the amygdala becomes coextensive with the ventral GP.

In addition, because the putamen projects to the GP, lesions restricted or localized to the putamen can also result in abnormal competition between atagonist and agonist muscles, due to the release of the GP (and associated neural circuitry) from putamen control. Patients or primates so effected suffer from severe dystonia as well as rigidity and increased muscle tone sometimes accompanied by chorea (Segawa, et al. 1987). Similarly, among those with Parkinson's disease, activity within the putamen is significantly reduced (Playford et al. 1992), and reduced functional activity is also seen in the caudate which merges with the putamen.


The GP receives about two thirds of its input from the putamen, and one third from the caudate (as well as some fibers from the SMA). Presumably, activation of the SMA -primary motor -caudate -putamen loop results in differential activation of the lateral and medial GP, the subthalamus, and the motor thalamus and the brainstem -nuclei which project back to the SMA and primary motor areas from which arises a massive rope of nerve fibers (the corticospinal/pyramidal tract) which directly innervates the brainstem and spinal cord. Presumably these complex feedback loops insure that coordinated and smooth continuous movements are planned, coordinated, and finally carried out. As noted, these interactions are also dependent on DA activity.

For example, Parkinson's disease, being characterized by reduced DA, is associated with a reduction in striatal inhibitory activity and thus increased GP output to the motor thalamus and brainstem which would produce tonic EMG activity and akinesia and rigidity (Kockgether, et al. 1986; Starr & Summerhayes, 1983); i.e. hypomovement due to excessive tonic excitation.

Conversely, excessive corpus stritatal DA would result in increased striatal GABA activity and thus inhibition of the GP which would lead to a disihibition of the motor thalamic and subthalamic nucleus and thus increased activation of brainstem and spinal motor neurons. Movements would become hyper, ballistic, and chorea may develop -as frequently occurs with prolonged neuroleptic treatment.

Specifically, GABA activity within the GP and subthalamus are significantly effected by DA activity within the corpus striatum. For example, deceases in striatal DA result in decreased striatal GABA neural activity (-which is normally inhibitory). As these GABA neurons project to the GP, the loss of this GABA inhibitory input would increase tonic activity within the GP. which in turn would result in increased inhibitory GP influences on the motor thalamus and brainstem thereby decreasing their activity. Hence, the modulatory influences of these latter nuclei on motor functioning would be eliminated, resulting in heightened activity levels and thus overactivation of this aspect of the feedback circuit. Brainstem and spinal motor neurons would become tonically activated thereby creating rigidity and stiffness of movement.

Conversely, the loss of GABA influences could induce choreic movements. In this regard it is noteworthy that significant GABA loss and abnormalities have been noted in the substantia nigra and basal ganglia of those with Huntington's chorea (Bird & Iversen, 1974), along with degeneration of the nigrostriatal DA projection pathway.

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