Basal Ganglia

Note:  Although the Basal Ganglia are part of the   Subcortical Brain ,  they interact very strongly with the Cerebral Cortex , when one is present.  Because we humans have a  Cerebral Cortex , research on the basal ganglia frequently focuses on it's interaction with the cerebral cortex and ignores it's interaction with other parts of the  Subcortical Brain .  For example,  Historical Background & Free Book claims:   
     "The frontal lobe of each hemisphere is responsible for planning and initiating sequences of behavior."  This is the majority view and represents a "top down" understanding of human behavior.   
    I will argue for a "bottom up" interpretation in which the frontal lobe plays an almost minor role in determining our behavior.  

Basal ganglia (Wiki)
    "The basal ganglia (or basal nuclei) are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. ... Currently popular theories implicate the basal ganglia primarily in action selection, that is, the decision of which of several possible behaviors to execute at a given time.[1][3] Experimental studies show that the basal ganglia exert an inhibitory influence on a number of motor systems  (
Tonic Inhibition ), and that a release of this inhibition permits a motor system to become active (Behavioral Disinhibition). The "behavior switching" that takes place within the basal ganglia is influenced by signals from many parts of the brain ..." 

Circuit connections
     "Specialized neurons from the primary motor cortex extend their axons all the way to the striatum portion of the basal ganglia. These cortical neurons release the neurotransmitter glutamate, which is excitatory in nature. Once excited by glutamate, the cells in the striatum project in two different directions giving rise to two major pathways: the "direct" and the "indirect" pathways:

    Connectivity diagram showing excitatory glutamatergic pathways as red, inhibitory GABAergic pathways as blue, and modulatory dopaminergic pathways as magenta.
    (Abbreviations: GPe: globus pallidus external; GPi: globus pallidus internal; STN: subthalamic nucleus;  SNc: Substantia Nigra pars Compacta;  SNr:  Substantia Nigra pars Reticulata). 

                GPl = Lateral Globus Pallidus = GPe: globus pallidus externa 
                GPm = Medial Globus Pallidus = GPi: globus pallidus interna  

    In the direct pathway, cortical cells project excitatory inputs to the striatum, which in turn projects inhibitory neurons onto the cells of the SNr-GPi complex. The SNr-GPi complex projects directly onto the thalamus through the inhibitory ansa lenticularis pathway. The striatal inhibition of the SNr-GPi complex coupled with SNr-GPi inhibition of the thalamus therefore results in a net reduction of inhibition of the thalamus via the striatum. ...
    The following diagram depicts the direct pathway:  

    Cortex (stimulates) → Striatum (inhibits) → "SNr-GPi" complex (less inhibition of thalamus) → Thalamus (stimulates) → Cortex (stimulates) → Muscles, etc. → (hyperkinetic state)

    The indirect pathway also starts from neurons in the striatum. Once stimulated by the cortex, striatal neurons in the indirect pathway project inhibitory axons onto the cells of the globus pallidus externa (GPe), which tonically inhibits the subthalamic nucleus (STN). This inhibition (by the striatum) of the inhibitory projections of the GPe, results in the net reduction of inhibition of the STN. The STN, in turn, projects excitatory inputs to the SNr-GPi complex (which inhibits the thalamus). The end-result is inhibition of the thalamus and, therefore, decreased stimulation of the motor cortex by the thalamus and reduced muscle activity. The direct and indirect pathways are therefore antagonist in their functions. Following is a diagram of the indirect pathway: 

    Cortex (stimulates) → Striatum (inhibits) → GPe (less inhibition of STN) → STN (stimulates) → "SNr-GPi" complex (inhibits) → Thalamus (is stimulating less) → Cortex (is stimulating less) → Muscles, etc. → (hypokinetic state) "   

    "The antagonistic functions of the direct and indirect pathways are modulated by the substantia nigra pars compacta (SNc), which produces dopamine. In the presence of dopamine, D1-receptors in the basal ganglia stimulate the GABAergic neurons, favoring the direct pathway, and thus increasing movement. The GABAergic neurons of the indirect pathway are stimulated by excitatory neurotransmitters acetylcholine and glutamate. This sets off the indirect pathway that ultimately results in inhibition of upper motor neurons, and less movement. In the presence of dopamine, D2-receptors in the basal ganglia inhibit these GABAergic neurons, which reduces the indirect pathways inhibitory effect. Dopamine therefore increases the excitatory effect of the direct pathway (causing movement) and reduces the inhibitory effect of the indirect pathway (preventing full inhibition of movement). Through these mechanisms the body is able to maintain balance between excitation and inhibition of motion. Lack of balance in this delicate system leads to pathologies such as Parkinson's disease. Parkinson's disease involves the loss of dopamine which means the direct pathway is less able to function (so no movement is initiated) and the indirect pathway is in overdrive (causing too much inhibition of movement)."   


I'm changing my notation.  Up until now,   
SNc >+ Str/NAC (DA-D1R)" 
meant that SNc used the neurotransmitter DA to communicate with the D1R receptor in the Str/NAC.  I'm going to change that notation to
    "SNc(DA)>+Str/NAC(D1R)" with the same meaning but less ambiguous.

    "Currently popular theories implicate the basal ganglia primarily in action selection; that is, it helps determine the decision of which of several possible behaviors to execute at any given time. In more specific terms, the basal ganglia's primary function is likely to control and regulate activities of the motor and premotor cortical areas so that voluntary movements can be performed smoothly.[1][3] Experimental studies show that the basal ganglia exert an inhibitory influence on a number of motor systems, and that a release of this inhibition permits a motor system to become active. The "behavior switching" that takes place within the basal ganglia is influenced by signals from many parts of the brain, including the prefrontal cortex, which plays a key role in executive functions.[2][4]   

    The main components of the basal ganglia are the striatum (caudate nucleus and putamen), the globus pallidus, the substantia nigra, the nucleus accumbens, and the subthalamic nucleus.[5] The largest component, the striatum, receives input from many brain areas but sends output only to other components of the basal ganglia. The pallidum receives input from the striatum, and sends inhibitory output to a number of motor-related areas. The substantia nigra is the source of the striatal input of the neurotransmitter dopamine, which plays an important role in basal ganglia function. The subthalamic nucleus receives input mainly from the striatum and cerebral cortex, and projects to the globus pallidus. Each of these areas has a complex internal anatomical and neurochemical organization.

The basal ganglia play a central role in a number of neurological conditions, including several movement disorders. The most notable are Parkinson's disease, which involves degeneration of the dopamine-producing cells in the substantia nigra pars compacta, and Huntington's disease, which primarily involves damage to the striatum.[1][5] Basal ganglia dysfunction is also implicated in some other disorders of behavior control such as Tourette syndrome, hemiballismus, obsessive–compulsive disorder, and Wilson's disease.

The basal ganglia have a limbic sector whose components are assigned distinct names: the nucleus accumbens, ventral pallidum, and ventral tegmental area. There is considerable evidence that this limbic part plays a central role in reward learning, particularly a pathway from the ventral tegmental area to the nucleus accumbens that uses the neurotransmitter dopamine. A number of highly addictive drugs, including cocaine, amphetamine, and nicotine, are thought to work by increasing the efficacy of this dopamine signal. There is also evidence implicating overactivity of the VTA dopaminergic projection in schizophrenia.[6]


Primate basal ganglia system (Wiki)
    "The basal ganglia form a major brain system in all species of vertebrates, but the basal ganglia of primates (including humans) have special features that justify a separate consideration. As in other vertebrates, the primate basal ganglia can be divided into striatal, pallidal, nigral, and subthalamic components. In primates, however, the two pallidal subdivisions are called the external and internal (or sometimes lateral and medial) segments of the globus pallidus, whereas in other species they are called the globus pallidus and entopeduncular nucleus. Also in primates, the striatum is divided by a large tract of white matter called the internal capsule into two masses of gray matter that early anatomists named the caudate nucleus and putamen—in most other species no such division exists, and only the striatum as a whole is recognized. Beyond this, the complex topography of connections between the striatum and cortex means that functions are segregated within the primate striatum in ways that do not apply to other species.
    A separate consideration of the primate basal ganglia is also warranted by the fact that different types of information are available than for other species. Large areas of the primate brain are devoted to vision; consequently the role of the basal ganglia in controlling eye movements has been studied almost exclusively in primates. Functional imaging studies have been performed mainly using human subjects. Also, several major degenerative diseases of the basal ganglia, including Parkinson's disease and Huntington's disease, are specific to humans, although "models" of them have been proposed for other species.


Basal ganglia: (Wiki)   
    Excellent 12 page PDF available online for free.
Very informative, but I wasn't able to copy the pictures.   
    "Some of the important "players" are the caudate nucleus and the putamen nucleus. Together they are called the neostriatum or simply striatum. Next to the putamen is the globus pallidus, and it can be seen to have two parts, a lateral (external or outer) segment and a medial (internal or inner) segment.   
    The putamen and globus pallidus, which lie adjacent to each other, are called the lenticular nucleus. Finally, the striatum and the globus pallidus are called the corpus striatum. You can also see a nice thick fiber bundle associated with the globus pallidus called the ansa lenticularis. This fasciculus passes under (ventral) the posterior limb of the internal capsule. While not apparent in this section, the ansa lenticularis then heads dorsally to reach the motor thalamic nuclei (VA/ VL). The ansa arises from cells of the inner segment of the globus pallidus and terminates in the ipsilateral VA/VL.   
    In addition to the ansa lenticularis, information from the globus pallidus can also reach the VA/VL via the lenticular fasciculus. This is not as simple as the ansa (called the jug handle). Globus pallidus fibers that pass into the lenticular fasiculus pass through (rather than under or ventral) the posterior limb of the internal capsule. We can see the lenticular fasciculus (levels 14 and15) caudal to where we see the ansa (level 16). The fibers in the lenticular fasciculus then pass a little caudally where they lie right on top of the subthalamic nucleus (level 14). The fibers in the lenticular fasciculus then suddenly loop dorsally and then pass rostrally towards the VA/VL (I told you it is not as simple as the jug handle). As the fibers comprising the lenticular fasciculus pass rostrally toward the VA/VL they join the cerebellothalamic (interpositus and dentate) fibers that are also headed for the VA/VL. This combined bundle (and another to be mentioned soon) is called the thalamic fasciculus.   
    Cortical inputs from all of the areas involved in the planning and execution of movements project to the striatum (caudate and putamen). Striatal neurons receiving these cortical inputs then project to the globus pallidus, which in turn projects to the VA/VL. VA/VL in turn projects to MI. So, the caudate, putamen and globus pallidus act on the motor thalamus, which acts on the motor cortex. There are no descending pathways that go directly to the spinal cord."  

Basal ganglia - Scholarpedia (Goog)       
Note:  This is a long and very interesting reference.  What follows is only a small part of it. 
    "Globus pallidus (internal)/entopeduncular nucleus

Globus pallidus (internal)/entopeduncular nucleus is one of the two output nuclei that receive inputs from other basal ganglia nuclei and provides output to external targets in the thalamus and brainstem. Thus, it receives inhibitory GABAergic afferents from the striatum and external globus pallidus, and excitatory glutamatergic input from the subthalamic nucleus. Neurones of the internal globus pallidus are GABAergic and exert powerful inhibitory effects on targets in the thalamus the lateral habenula and the brainstem (Parent et al. 1999).

     Substantia nigra pars reticulata

Substantia nigra pars reticulata is the second principal output nucleus also receiving afferents from other basal ganglia nuclei and providing efferent connections to the thalamus and brainstem. Inhibitory (GABAergic) inputs come from the striatum and globus pallidus (external) and excitatory input from the subthalamus (Gerfen and Wilson 1996). Pars reticulata neurones are also GABAergic and impose strong inhibitory control over parts of the thalamus and brainstem, including the superior colliculus, pedunculopontine nucleus and medullary reticular formation (Chevalier and Deniau 1990).

     Globus pallidus (external)

Globus pallidus (external) is the principal "intrinsic" structure of the basal ganglia since it's major connections are with other basal ganglia nuclei. Thus, it receives inhibitory input from the striatum, excitatory input from the subthalamus, and provides GABAergic inhibitory efferent connections to all the basal ganglia's input and output nuclei (Chan et al. 2005). It also provides inhibitory input to the SNc (Parent et al. 1999). "

1988 10<13
Synaptic organization of the striatum   
    "The striatum, the main component of the basal ganglia, is composed of mainly one type of neuron, the so-called medium spiny neuron. This neuron cell type, which constitutes over 90% of striatal neurons, is the major output neuron of the striatum.  Combined ultrastructural neuroanatomical methods have elucidated the organization of afferent connectivity to these neurons.  
    The major physiologic function of striatal efferent activity appears to be inhibition of tonically active GABAergic neurons in the globus pallidus and substantia nigra pars reticulata."   
   See:  Medium Spiny Neurons  

GABAergic output of the basal ganglia. 
Using GABAergic outputs from the SNr or GP(i), the basal ganglia exert inhibitory control over several motor areas in the brainstem which in turn control the central pattern generators for the basic motor repertoire including eye-head orientation, locomotion, mouth movements, and vocalization. 
    These movements are by default kept suppressed by tonic rapid firing of SNr/GP(i) neurons, but can be released by a selective removal of the tonic inhibition. Derangement of the SNr/GP(i) outputs leads to either an inability to initiate movements (akinesia) or an inability to suppress movements (involuntary movements). Although the spatio-temporal patterns of individual movements are largely innate and fixed, it is essential for survival to select appropriate movements and arrange them in an appropriate order depending on the context, and this is what the basal ganglia presumably do. To achieve such a goal, however, the basal ganglia need to be trained to optimize their outputs with the aid of cortical inputs carrying sensorimotor and cognitive information and dopaminergic inputs carrying reward-related information. The basal ganglia output to the thalamus, which is particularly developed in primates, provides the basal ganglia with an advanced ability to organize behavior by including the motor skill mechanisms in which new movement patterns can be created by practice. To summarize, an essential function of the basal ganglia is to select, sort, and integrate innate movements and learned movements, together with cognitive and emotional mental operations, to achieve purposeful behaviors. Intricate hand-finger movements do not occur in isolation; they are always associated with appropriate motor sets, such as eye-head orientation and posture."   
    325 Related citations: 
    29 Cited by's: 
    My comment:   
The "SNr/GP(i) outputs" are what the Wikipedia article, above, calls the "SNr-GPi complex" and part of the "direct pathway". 

Evolutionary conservation of the basal ganglia as a common vertebrate mechanism for action selection.      
Free Article   
Although the basal ganglia are thought to play a key role in action selection in mammals, it is unknown whether this mammalian circuitry is present in lower vertebrates as a conserved selection mechanism. We aim here, using lamprey, to elucidate the basal ganglia circuitry in the phylogenetically oldest group of vertebrates (cyclostomes) and determine how this selection architecture evolved to accommodate the increased behavioral repertoires of advanced vertebrates.   
We show, using immunohistochemistry, tract tracing, and whole-cell recordings, that all parts of the mammalian basal ganglia (striatum, globus pallidus interna [GPi] and externa [GPe], and subthalamic nucleus [STN]) are present in the lamprey forebrain. In addition, the circuit features, molecular markers, and physiological activity patterns are conserved. Thus, GABAergic striatal neurons expressing substance P project directly to the pallidal output layer, whereas enkephalin-expressing striatal neurons project indirectly via nuclei homologous to the GPe and STN. Moreover, pallidal output neurons tonically inhibit tectum, mesencephalic, and diencephalic motor regions.   
These results show that the detailed basal ganglia circuitry is present in the phylogenetically oldest vertebrates and has been conserved, most likely as a mechanism for action selection used by all vertebrates, for over 560 million years. Our data also suggest that the mammalian basal ganglia evolved through a process of exaptation, where the ancestral core unit has been co-opted for multiple functions, allowing them to process cognitive, emotional, and motor information in parallel and control a broader range of behaviors."
    111 Related citations:
    27 Cited by's:
    Free full text:

Basal ganglia: insights into origins from lamprey brains.
"The lamprey brain has now been shown to have basal ganglia circuitry, with an output that acts tonically on midbrain and brainstem motor centers and is modulated by ascending dopaminergic input. This condition was believed to represent the tetrapod condition, but now appears to be far more ancient."
    92 Related citations:
    Free Full Text:
    2 Cited by's:

Evolution of the basal ganglia: dual-output pathways conserved throughout vertebrate phylogeny.  
    The basal ganglia, including the striatum, globus pallidus interna and externa (GPe), subthalamic nucleus (STN), and substantia nigra pars compacta, are conserved throughout vertebrate phylogeny and have been suggested to form a common vertebrate mechanism for action selection. 
     In mammals, this circuitry is further elaborated by the presence of a dual-output nucleus, the substantia nigra pars reticulata (SNr), and the presence of modulatory input from the cholinergic pedunculopontine nucleus (PPN).  
    We sought to determine whether these additional components of the mammalian basal ganglia are also present in one of the phylogenetically oldest vertebrates, the lamprey. We show, by using immunohistochemistry, tract tracing, and whole-cell recordings, that homologs of the SNr and PPN are present in the lamprey. Thus the SNr receives direct projections from inwardly rectifying γ-aminobutyric acid (GABA)-ergic striatal neurons expressing substance P, but it is also influenced by indirect basal ganglia projections from the STN and potentially the GPe.  
    Moreover, GABAergic SNr projection neurons are tonically active and project to the thalamus and brainstem motor areas.  
     The homolog of the PPN contains both cholinergic and GABAergic neurons and is connected with all the nuclei of the basal ganglia, supporting its proposed role as part of an extended basal ganglia. A separate group of cholinergic neurons dorsal to the PPN corresponds to the descending mesencephalic locomotor region. Our results suggest that dual-output nuclei are part of the ancestral basal ganglia and that the PPN appears to have coevolved as part of a mechanism for action selection common to all vertebrates."  
    17 Cited by's:   

The evolutionary origin of the vertebrate basal ganglia and its role in action selection.    
    "The group of nuclei within the basal ganglia of the forebrain is central to the control of movement.    
    We present data showing that the structure and function of the basal ganglia have been conserved throughout vertebrate evolution over some 560 million years. The interaction between the different nuclei within the basal ganglia is conserved as well as the cellular and synaptic properties and transmitters.  
    We consider the role of the conserved basal ganglia circuitry for basic patterns of motor behaviour controlled via brainstem circuits. The output of the basal ganglia consists of tonically active GABAergic neurones, which target brainstem motor centres responsible for different patterns of behaviour, such as eye and locomotor movements, posture, and feeding.  
    A prerequisite for activating or releasing a motor programme is that this GABAergic inhibition is temporarily reduced. This can be achieved through activation of GABAergic projection neurons from striatum, the input level of the basal ganglia, given an appropriate synaptic drive from cortex, thalamus and the dopamine system. The tonic inhibition of the motor centres at rest most likely serves to prevent the different motor programmes from becoming active when not intended.  
     Striatal projection neurones are subdivided into one group with dopamine 1 receptors that provides increased excitability of the direct pathway that can initiate movements, while inhibitory dopamine 2 receptors are expressed on neurones that instead inhibit movements and are part of the 'indirect loop' in mammals as well as lamprey.  
    We review the evidence showing that all basic features of the basal ganglia have been conserved throughout vertebrate phylogeny, and discuss these findings in relation to the role of the basal ganglia in selection of behaviour."  

Independent circuits in the basal ganglia for the evaluation and selection of actions.         
    "The basal ganglia are critical for selecting actions and evaluating their outcome. Although the circuitry for selection is well understood, how these nuclei evaluate the outcome of actions is unknown.  
    Here, we show in lamprey that a separate evaluation circuit, which regulates the habenula-projecting globus pallidus (GPh) neurons, exists within the basal ganglia. The GPh neurons are glutamatergic and can drive the activity of the lateral habenula, which, in turn, provides an indirect inhibitory influence on midbrain dopamine neurons.  
    We show that GPh neurons receive inhibitory input from the striosomal compartment of the striatum. The striosomal input can reduce the excitatory drive to the lateral habenula and, consequently, decrease the inhibition onto the dopaminergic system.  
    Dopaminergic neurons, in turn, provide feedback that inhibits the GPh. In addition, GPh neurons receive direct projections from the pallium (cortex in mammals), which can increase the GPh activity to drive the lateral habenula to increase the inhibition of the neuromodulatory systems.  
    This circuitry, thus, differs markedly from the "direct" and "indirect" pathways that regulate the pallidal (e.g., globus pallidus) output nuclei involved in the control of motion. Our results show that a distinct reward-evaluation circuit exists within the basal ganglia, in parallel to the direct and indirect pathways, which select actions. Our results suggest that these circuits are part of the fundamental blueprint that all vertebrates use to select actions and evaluate their outcome. " 

The activity in the dopaminergic reward system of the brain is concerned with the evaluation of actions and is controlled from the lateral habenulae, in all vertebrates investigated, from lamprey to primates. This study considers the mechanisms by which the lateral habenulae is controlled. We show here that a particular group of nerve cells conveys excitatory drive to the lateral habenulae, which, in turn, receive excitatory input from pallium (cortex in mammals) and inhibitory control from a specific compartment (striosomes) in the basal ganglia. This control system is critical for value-based decisions, important in all groups of vertebrates." 


Electrophysiological characterization of entopeduncular nucleus neurons in anesthetized and freely moving rats.  
The EntoPeduncular nucleus (EP), which is homologous to the internal segment of the Globus Pallidus (GPi) in primates, is one of the two basal ganglia (BG) output nuclei. Despite their importance in cortico-BG information processing"    

Evolutionary and developmental contributions for understanding the organization of the basal ganglia. 
    These data show that the globus pallidus of rodents contains two major subpopulations of GABAergic projection neurons:
    (1) neurons containing parvalbumin and neurotensin-related hexapetide (LANT6), with descending projections to the subthalamus and substantia nigra, which originate from progenitors expressing Nkx2.1, primarily located in the pallidal embryonic domain (medial ganglionic eminence), and  
    (2) neurons containing preproenkephalin (and possibly calbindin), with ascending projections to the striatum, which appear to originate from progenitors expressing Islet1 in the striatal embryonic domain (lateral ganglionic eminence). Based on data on Nkx2.1, Islet1, LANT6 and proenkephalin, it appears that both cell types are also present in the globus pallidus/dorsal pallidum of chicken, frog and lungfish."

2015      2<349
The basal ganglia downstream control of brainstem motor centres--an evolutionarily conserved strategy.  

The basal ganglia plays a crucial role in decision-making and control of motion. The output of the basal ganglia consists of tonically active GABAergic neurons, a proportion of which project to different brainstem centres and another part projecting to thalamus and back to cortex. The focus here is on the former part, which keeps the different brainstem motor-centres tonically inhibited under resting conditions. These centres will be disinhibited when called into action. In the control of motion the direct pathway will promote movement and the indirect pathway inhibit competing movement patterns counteracting the motor-command issued. The basal ganglia detailed structure and function are conserved throughout the vertebrate evolution, including the afferent (e.g. habenulae) and efferent control of the dopamine system. "  

2016  2<17 
    The Basal Ganglia Over 500 Million Years 
    The lamprey belongs to the phylogenetically oldest group of vertebrates that diverged from the mammalian evolutionary line 560 million years ago. A comparison between the lamprey and mammalian basal ganglia establishes a detailed similarity regarding its input from cortex/pallium and thalamus, as well as its intrinsic organisation and projections of the output nuclei.     
    This means that the basal ganglia circuits now present in rodents and primates most likely had evolved already at the dawn of vertebrate evolution. This includes the 'direct pathway' with striatal projection neurons (SPNs) expressing dopamine D1 receptors, which act to inhibit the tonically active GABAergic output neurons in globus pallidus interna and substantia nigra pars reticulata that at rest keep the brainstem motor centres under tonic inhibition.  
    The 'indirect pathway' with dopamine D2 receptor-expressing SPNs and intrinsic basal ganglia nuclei is also conserved. The net effect of the direct pathway is to disinhibit brainstem motor centres and release motor programs, while the indirect pathway instead will suppress motor activity.      
    Transmitters, connectivity and membrane properties are virtually identical in lamprey and rodent basal ganglia.     
    We predict that the basal ganglia contains a series of modules each controlling a given pattern of behaviour including locomotion, eye-movements, posture, and chewing that contain both the direct pathway to release a motor program and the indirect pathway to inhibit competing behaviours.      
    The phasic dopamine input serves value-based decisions and motor learning. During vertebrate evolution with a progressively more diverse motor behaviour, the number of modules will have increased progressively. These new modules with a similar design will be used to control newly developed patterns of behaviour - a process referred to as exaptation.      Free full text 

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