Synaptic targets of the intrinsic axon collaterals of supragranular pyramidal neurons in monkey prefrontal cortex

The principal axons of supragranular pyramidal neurons in the cerebral cortex travel through the white matter and terminate in other cortical areas, whereas their intrinsic axon collaterals course through the gray matter and form both local and long-distance connections within a cortical region. In the monkey prefrontal cortex (PFC), horizontally oriented, intrinsic axon collaterals from supragranular pyramidal neurons form a series of stripe-like clusters of axon terminals (Levitt et al. [1993] J Comp Neurol 338:360-376; Pucak et al. [1996] J Comp Neurol 376:614-630). The present study examined the synaptic targets of the intrinsic axon collaterals arising from supragranular pyramidal neurons within the same stripe (local projections). Approximately 50% of the within-stripe axon terminals in monkey PFC area 9 targeted dendritic spines. In contrast, for both the intrinsic axon collaterals that travel between stripes (long-range projections), and the axon terminals that project to other PFC areas (associational projections), over 92% of the postsynaptic structures were dendritic spines (Melchitzky et al. [1998] J Comp Neurol 390:211-224). The other 50% of the within-stripe terminals synapsed with dendritic shafts. Dual-labeling studies confirmed that these within-stripe terminals contacted gamma-aminobutyric acid-immunoreactive dendritic shafts, including the subpopulation that contains the calcium-binding protein parvalbumin. The functional significance of the differences in synaptic targets between local and long-range intrinsic axon collaterals was supported by whole-cell, patch clamp recordings in an in vitro slice preparation of monkey PFC. Specifically, the small amplitude responses observed in layer 3 pyramidal neurons during long-range, low-intensity stimulation were exclusively excitatory, whereas local stimulation also evoked di/polysynaptic inhibitory responses. These anatomic and electrophysiological findings suggest that intrinsic connections of the PFC differ from other cortical regions and that within the PFC, feedback (within-stripe) inhibition plays a greater role in regulating the activity of supragranular pyramidal neurons than does feedforward inhibition either between stripes or across regions.     

Pyramidal cell loss in motor cortices in Huntington's disease

Patterns of huntingtin protein aggregation and cortical neuronal loss suggest early involvement of corticostriatal pathways in Huntington's disease. However, theories of pathogenesis of chorea rely on the motor cortices being intact. The motor cortices have not previously been studied at a cellular level in Huntington's disease. We analyzed the neuronal number in the caudate, putamen, and three motor cortical areas in five cases of Huntington's disease and five controls. For each motor cortical region the total neuronal number, number of interneurons, and number of SMI32 immunopositive pyramidal neurons were quantified using previously published techniques and any relationship between cell loss and severity or duration of chorea was examined. The results showed a loss of long projecting SMI32 immunopositive pyramidal neurons in the primary motor cortex with associated morphological changes and suggest a loss of short projecting pyramidal neurons in the premotor cortex. Degeneration in the primary motor cortex correlated with subcortical degeneration. These findings indicate pyramidal cell involvement in Huntington's disease and implicate the degeneration of corticostriatal pathways in the production of chorea.     

Synaptic relationships involving local axon collaterals of pyramidal neurons in the cat motor cortex

The intracortical synaptic relationships of pyramidal neurons in the cat motor cortex were studied by intracellular recording and labeling techniques. Neurons that responded with monosynaptic excitatory postsynaptic potentials (EPSPs) to microstimulation in the somatosensory cortex were identified by intracellular recordings. Long-term potentiation (LTP) was evoked in all of these neurons (n = 15), following tetanic stimulation (50 Hz, 5 s) of their afferents from the somatosensory cortex. Three of these cells (cells A-C) were identified as pyramidal neurons, following intracellular injections of Neurobiotin. The intracortical axon collaterals of these labeled cells arborized extensively, forming terminal clusters both in clse proximity to the parent soma and along their long, horizontal branches. Terminal clusters in both the proximal and in the distal termination zones of each of the cells were studied by electron microscopy. In their proximal arborization zones, the axon collaterals of the labeled pyramidal neurons synapsed preferentially with dendritic spines belonging to other pyramidal cells. In contrast, in their distal terminal clusters, the axon collateals of each of the cells formed synapses in different proportions with different postsynaptic targets. The distal axon collaterals of cell A formed 86% of their synapses with pyramidal neurons; those of cell B formed 64% of their synapses with pyramidal cells, the remaining synapses with the dendritic shafts and somata of nonpyramidal neurons, and those of cell C provided most of their output (68%) to nonpyramidal, presumably inhibitory neurons. These findings suggest a high selectivity of intrinsic axon collaterals to form specific patterns of synapses. The patterns of synaptic interactions formed by these intrinsic axon collaterals may be a substrate for shaping and modulating representation maps in the motor cortex. © 1993 Wiley-Liss, Inc.     

State-dependent spike and local field synchronization between motor cortex and substantia nigra in hemiparkinsonian rats

Excessive beta frequency oscillatory and synchronized activity has been reported in the basal ganglia of parkinsonian patients and animal models of the disease. To gain insight into processes underlying this activity, this study explores relationships between oscillatory activity in motor cortex and basal ganglia output in behaving rats after dopamine cell lesion. During inattentive rest, 7 d after lesion, increases in motor cortex-substantia nigra pars reticulata (SNpr) coherence emerged in the 8-25 Hz range, with significant increases in local field potential (LFP) power in SNpr but not motor cortex. In contrast, during treadmill walking, marked increases in both motor cortex and SNpr LFP power, as well as coherence, emerged in the 25-40 Hz band with a peak frequency at 30-35 Hz. Spike-triggered waveform averages showed that 77% of SNpr neurons, 77% of putative cortical interneurons, and 44% of putative pyramidal neurons were significantly phase-locked to the increased cortical LFP activity in the 25-40 Hz range. Although the mean lag between cortical and SNpr LFPs fluctuated around zero, SNpr neurons phase-locked to cortical LFP oscillations fired, on average, 17 ms after synchronized spiking in motor cortex. High coherence between LFP oscillations in cortex and SNpr supports the view that cortical activity facilitates entrainment and synchronization of activity in basal ganglia after loss of dopamine. However, the dramatic increases in cortical power and relative timing of phase-locked spiking in these areas suggest that additional processes help shape the frequency-specific tuning of the basal ganglia-thalamocortical network during ongoing motor activity.     

Arm trajectory and representation of movement processing in motor cortical activity

We review experiments in which single-cell primary motor cortical activity was recorded from Rhesus monkeys (Macaca mulatta) while they performed reaching and drawing tasks. The directional tuning curves generated during reaching were modulated by the speed of movement and this was reflected in the magnitude of population vectors calculated from firing rates of a large population of cells. Directional and speed representation in the firing rates of these cells is robust across both reaching and drawing. Several behavioural invariants related to the speed of drawing were represented in the time-series of population vectors. This high fidelity neural representation of velocity found in motor cortex can be used to visualize the dynamics of motor cortical activity during drawing and suggests that the cost function governing the rate of drawing is bound by neural processing.     

Morphological studies on interneuronal relations in the feline motor cortex]

Three types of neuronal joinings in the cat motor cortex are described. The joinings of the 1st type (nests, barrels) consist of some pyramidal cells, apical dendrites of which form the bundles. The consolidation of neurons is achieved by means of dendro-dentritic contacts, pyramidal neuron collaterals and the associative transcortical afferents. The joinings of the 2nd type (distant) are formed with the participation of intracortical connections between the pyramidal and stellate neurons and are placed as concentric formation. The joinings of the 3rd type are formed with the help of projection thalamo-cortical afferents and large horizontal collaterals of basket cells.     

In vitro characterization of intrinsic properties and local synaptic inputs to pyramidal neurons in macaque primary motor cortex

Primates (including humans) have a highly developed corticospinal tract, and specialized motor cortical areas which differ in key ways from rodents. Much work on motor cortex has therefore used macaque monkeys as a good animal model for human motor control. However, there is a paucity of data describing the fundamental functional architecture of primate primary motor cortex, which is best addressed with in vitro approaches. In this study we examined the cellular properties and the micro‐circuitry of the adult macaque primary motor cortex by carrying out in‐vitro intracellular recordings. We aimed to characterize the basic properties of the cortical circuitry by studying the intrinsic properties of its pyramidal neurons and their physiological interconnectivity. We studied the passive and active electrophysiological properties of pyramidal neurons in both superficial and deep cortical layers. Both superficial and deep pyramidal neurons exhibited bursting behaviour that could act as powerful excitation for downstream targets. Synaptic connections were lamina specific. Neurons in the deep layers had convergent excitatory inputs from all cortical layers whereas superficial neurons had only significant inputs from superficial layers. This sheds light on the functional architecture of the primate primary motor cortex and how its output is shaped. We also took the unique opportunity in our recording technique to characterize the relationship between intracellular and extracellular spike waveforms, with implications for cell‐type identification in studies in awake behaving monkey. Our results will aid the interpretation of primate studies into motor control involving extracellular spike recordings and electrical stimulation in primary motor cortex.     

Intracortical distribution of axonal collaterals of pyramidal tract cells in the cat motor cortex

Slow and fast pyramidal tract cells (Pt cells) from the cat motor cortex were identified antidromically and injected with horseradish peroxidase (HRP). The axonal collaterals of these cells were mapped following HRP histochemistry with benzidine di-hydrochloride. All cells, slow or fast, show a similar arrangement of their collaterals. A proximal axonal network of 0.5–0.8 mm in diameter delimits a local field of action for collaterals in layers V and VI. The tangential expansion of this local field corresponds to that of the basal dendritic domain of Pt neurons. Much longer collaterals running for millimeters in the lower gray or white matter were observed in all cells. They form at a cortical level a distal field of action for Pt neurons. Many of these long branches were traced to other regions of area 4 or toward other cytoarchitectonic areas. In one case a collateral was seen entering and dividing in area 3a. Due to limitations of the HRP technique most of these long branches could not be followed to their terminals. On the basis of the laminar distribution of Pt cell collaterals (mostly in layers V and VI) synaptic sites where recurrent excitation and inhibition are produced on Pt neurons are discussed.     

Organization of the mouse motor cortex studied by retrograde tracing and intracortical microstimulation (ICMS) mapping

The motor representation of the body musculature was studied in 11 adult mice by using ICMS. The motor responses elicited from both granular and agranular cortical fields showed that the mouse motor cortex is topographically organized; however, within the representation of individual body-parts the movements are multiply represented. In addition, several sites were encountered where more than one movement was elicited at the same stimulus threshold. The locations of pyramidal cells contributing axons to the pyramidal tract were examined by means of retrograde tracing with HRP injected into the cervical enlargement. This procedure labeled neurons only in lamina V in granular and agranular cortical fields. The similarities between the organization of motor cortex demonstrated in this study and the organization in the rat suggest that the rat and mouse share a common plan of rodent motor cortical organization.     

Effects of low frequency and low intensity repetitive paired pulse stimulation of the primary motor cortex.

OBJECTIVE: Following a previous report [Bestmann et al. Clin Neurophysiol 2004;115:755-64] that pairs of subthreshold pulses of transcranial magnetic stimulation (TMS) can show temporal summation, we explored whether repeated application of pairs of stimulation could produce long-lasting after effects on the excitability of the human motor cortex. METHODS: Twelve healthy subjects received 25 min repetitive paired pulse magnetic stimulation (paired rTMS) given at a frequency of about 0.6 Hz over the left primary motor cortex (500 paired stimuli in total). The interval between the paired stimuli was 3 ms and the intensity of both stimuli was 80% of active motor threshold. The resting and active motor threshold, MEP recruitment curve, short interval intracortical inhibition (SICI) and facilitation, and the duration of the cortical silent period (SP) were tested for the right first interosseous muscle (FDI) before and two times after the end of 25 min paired rTMS. RESULTS: Prolonged subthreshold paired rTMS produced a significant decrease in excitability in the corticospinal projection to FDI: resting motor threshold was significantly increased and MEP recruitment was significantly decreased, SICI was significantly increased at 2 and 4 ms and the SP was significantly increased in duration. CONCLUSIONS: Prolonged low frequency paired rTMS at subthreshold intensity can modulate cortical excitability by producing inhibitory effects that outlast the period of stimulation.     

Predominant information transfer from layer III pyramidal neurons to corticospinal neurons

Connections of layer III pyramidal neurons to corticospinal neurons of layer V and corticothalamic neurons of layer VI in the rat primary motor cortex were examined in brain slices by combining intracellular staining with Golgi-like retrograde labeling of corticofugal neurons. Forty layer III pyramidal neurons stained intracellularly were of the regular-spiking type, showed immunoreactivity for glutaminase, and emitted axon collaterals arborizing locally in layers II/III and/or V. Nine of them were reconstructed for morphologic analysis; 15.2% or 3.8% of varicosities of axon collaterals of the reconstructed neurons were apposed to dendrites of corticospinal or corticothalamic neurons, respectively. By confocal laser scanning and electron microscopy, some of these appositions were revealed to make synapses. These findings suggest that corticospinal neurons receive information from the superficial cortical layers four times more frequently than corticothalamic neurons. The connections were further examined by intracellular recording of excitatory postsynaptic potential (EPSP) that were evoked in layer V and layer VI pyramidal neurons by stimulation of layer II/III. EPSPs evoked in layer V pyramidal neurons showed short and constant onset latencies, suggesting their monosynaptic nature. In contrast, most EPSPs evoked in layer VI pyramidal neurons had long onset latencies, showed double-shock facilitation of onset latency, and were largely suppressed by an N-methyl-D-aspartic acid receptor blocker, suggesting that they were polysynaptic. The results suggest that information from the superficial cortical layers is transferred directly and efficiently to corticospinal neurons in layer V and thereby exerts an important influence on cortical motor output. Corticothalamic neurons are, in contrast, considered relatively independent of, or indirectly related to, information processing of the superficial cortical layers.     

Modulation of spinal excitability during observation of hand actions in humans

There is growing evidence that observation of actions performed by other individuals activates observer's cortical motor areas. This matching of observed actions on the observer's motor repertoire could be at the basis of action recognition. Here we investigated if action observation, in addition to cortical motor areas, involves also low level motor structures mimicking the observed actions as if they were performed by the observer. Spinal cord excitability was tested by eliciting the H-reflex in a finger flexor muscle (flexor digitorum superficialis) in humans looking at goal-directed hand actions presented on a TV screen. We found that, in the absence of any detectable muscle activity, there was in the observers a significant modulation of the monosynaptic reflex size, specifically related to the different phases of the observed movement. The recorded H-reflex rapidly increased in size during hand opening, it was depressed during hand closing and quickly recovered during object lifting. This modulation pattern is, however, opposite to that occurring when the recorded muscles are actually executing the observed action [Lemon et al. (1995) J. Neurosci., 15, 6145-56]. Considering that, when investigated at cortical level the modulation pattern of corticospinal excitability replicates the observed movements [Fadiga et al. (1995) J. Neurophysiol., 73, 2608-2611], this spinal 'inverted mirror' behaviour might be finalised to prevent the overt replica of the seen action.     

Patterns of neuronal degeneration in the motor cortex of amyotrophic lateral sclerosis patients

Summary We examined patterns of neuronal degeneration in the motor cortex of amyotrophic lateral selerosis (ALS) patients using traditional cell stains and several histochemical markers including neurofilament, parvalbumin, NADPH-diaphorase, ubiquitin, Alz-50 and tau. Three grades of ALS (mild, moderate, severe) were defined based on the extent of Betz cell depletion. Non-phosphorylated neurofilament immunoreactive cortical pyramidal neurons and non-pyramidal parvalbumin local circuit neurons were significantly depleted in all grades of ALS. In contrast, NADPH-diaphorase neurons and Alz-50-positive neurons were quantitatively preserved despite reduced NADPH-diaphorase cellular staining and dendritic pruning. The density of ubiquitin-positive structures in the middle and deep layers of the motor cortex was increased in all cases. Axonal tau immunoreactivity was not altered. These histochemical results suggest that cortical degeneration in ALS is distinctive from other neurodegenerative diseases affecting cerebral cortex. Unlike Huntington's disease, both pyramidal and local cortical neurons are affected in ALS; unlike Alzheimer's disease, alteration of the neuronal cytoskeleton is not prominent. The unique pattern of neuronal degeneration found in ALS motor cortex is consistent with non-N-methyl-Dxxx-aspartate glutamate receptor-mediated cytotoxicity.Supported in part by a Muscular Dystrophy Association Research Development grant     

The role of ipsilateral primary motor cortex in movement control and recovery from brain damage

The role of ipsilateral motor areas for movement control is not yet fully understood. The relevance of these areas to the recovery of motor function following a brain lesion is a matter of dispute. It has recently been stated that increased ipsilateral activation following brain damage is maladaptive and hindering the process of recovery. Others have presented evidence that ipsilateral motor areas subserve motor recovery.A recent study published in Experimental Neurology [Lotze, M., Sauseng, P., Staudt, M., 2009. Functional relevance of ipsilateral motor activation in congenital hemiparesis as tested by fMRI-navigated TMS. Exp. Neurol., 217, 440-443.] on patients with congenital hemiparesis presents evidence for the importance of ipsilateral primary motor cortex and dorsal premotor cortex to movement control even in the absence of direct ipsilateral descending output in this special set of patients.This comment briefly summarizes the relevant findings supporting both views and discusses potential causes for the prima facie contradictory findings.     

Glutamate receptor expression and chronic glutamate toxicity in rat motor cortex

In addition to the loss of spinal motor neurons, amyotrophic lateral sclerosis (ALS) is also associated with degeneration of corticospinal layer V pyramidal neurons and decreased glutamate transport in the cortex. We characterized the glutamate receptors on corticospinal neurons in acutely isolated rat motor cortex slices and found that the synaptic inputs to the corticospinal layer V neurons had a lesser proportional contribution from NMDA receptors relative to AMPA receptors than did layer II/III pyramidal neurons. The synaptic I(AMPA) was also more inwardly rectified, indicating a greater Ca(2+)-permeable component, in layer V. In a cortical organotypic slice culture model, blockade of glutamate transporters elevated glutamate in the media and led to pyramidal neuron loss in both layers. The loss of layer V pyramidal neurons was attenuated by antagonists of AMPA/kainate or Ca(2+)-permeable AMPA receptors, suggesting their therapeutic potential in the protection of the motor cortex in ALS.     

Percutaneous electric and magnetic stimulation of the motor cortex in man. Physiological aspects and clinical applications

The new techniques of percutaneous electric and magnetic stimulation of the motor cortex in conscious man provide a unique opportunity of functional testing of the central motor pathways. These techniques seem to be safe and no immediate or delayed adverse reactions have been reported. The physiological studies so far performed suggest that the structures which are preferentially excited by these methods are the fast conducting pyramidal neurones. It has been shown that a single cortical stimulus is able to activate spinal motoneurones repeatedly. This phenomenon can easily be explained if the cortical stimulus generates multiple descending volleys in the central motor pathways. By comparison with experiments of stimulation of the exposed motor cortex in animals, it is likely that electric brain stimulation directly activates the axons of the pyramidal neurons at their origin and to a lesser extent also recruits these neurons transsynaptically, via some cortical interneurones. Magnetic stimulation of the brain at the vertex seems to act mostly by the latter mechanism. These different modes of action of the two methods of cortical stimulation explain the latency differences of the EMG responses obtained with either technique. Increased excitability of the spinal motoneurones and the existence of multiple descending volleys in response to a single cortical stimulus result in shortening of the latencies and greater amplitude of the responses recorded during voluntary contraction of the target muscle. Stimulation of the motor cortex has been used in pilot studies conducted on patients suffering from various disorders of the central motor pathways, such as multiple sclerosis, cervical spondylosis, motor neurone disease or stroke. The sensitivity of the technique looks promising. In M.S., the EMG responses usually show an increased central conduction latency, a reduced amplitude and a prolonged duration. The severity of the electrophysiological abnormalities is not very well correlated with clinical weakness, but the correlations seems to be better with hyperreflexia and the presence of brisk finger flexor jerks. The same abnormalities are observed in cervical spondylosis, although to a lesser extent. In motor neurone disease, the responses have a moderately increased latency and their size and duration are markedly reduced. Patients with acute hemispheric stroke usually show absent responses on the contralateral side. Finally, electric cortical stimulation can be very useful in monitoring the functional integrity of descending motor tracts during surgical operations performed on the spinal cord.     

Selective elimination of axons extended by developing cortical neurons is dependent on regional locale: experiments utilizing fetal cortical transplants

In adult rats, cortical neurons that extend an exon through the pyramidal tract (a major subcortical efferent projection of the neocortex) are limited to layer V of about the rostral two-thirds of the neocortex. In neonates, however, pyramidal tract neurons are distributed throughout the neocortex, but all of those found in certain areas, such as the posterior occipital region (including primary visual cortex) selectively lose their pyramidal tract axon (Stanfield et al., 1982) yet maintain axon collaterals to other subcortical targets (O'Leary and Stanfield, 1985). To determine if the regional location of a developing pyramidal tract neuron critically influences the maintenance or elimination of the axon collaterals it initially extends, pieces of cortex from embryonic day 17 (E17) rat fetuses (exposed to 3H-thymidine on E15) were transplanted heterotopically into the cortex of newborn (PO) rats; rostral cortex was placed into the posterior occipital region (R----O), or posterior occipital cortex into a rostral cortical locale (O----R). The retrograde tracers Fast blue (FB) and Diamidino yellow (DY) were used to assay for the presence of specific populations of cortical projection neurons within the autoradiographically identified transplants. In terms of the extension and maintenance of pyramidal tract axons, the transplanted neurons behave like the host neurons of the recipient cortical region rather than like those of their site of origin. At P40, following FB injections into the pyramidal decussation on P34, pyramidal tract neurons are labeled within the O----R transplants, but none can be labeled within R----O transplants, although in the same R----O cases transplanted neurons are labeled by an injection of DY in the superior colliculus. However, at P13 pyramidal tract neurons can be identified within the R----O transplants, as well as in the host occipital cortex, following injections made on P9, a period when the distribution of pyramidal tract neurons in normal rats is widespread (Stanfield and O'Leary, 1985b). In a second series of host rats, on P34 FB was injected in the pyramidal decussation of the O----R cases, or in the superior colliculus of the R----O cases, and in both groups DY was injected into the region of contralateral cortex homotopic for the new location of the transplant. On P40, in both the O----R and R----O transplants, many neurons singly labeled with FB or DY are found, but no double dye-labeled cells are seen.(ABSTRACT TRUNCATED AT 400 WORDS)     

Asymmetries between dominant and non-dominant hands in real and imagined motor task performance

Motor imagery is a dynamic state in which an individual mentally simulates the performance of a specific motor action or motor task. Recent behavioural and neuroimaging evidence suggests that the same neurocognitive networks control real and imagined movements. This hypothesis was tested by investigating whether motor asymmetries related to cerebral dominance also occurred for imagined movements. Fifty subjects performed the visually guided pointing task of Sirigu et al. [Sirigu, A., Duhamel, J., Cohen, L., Pillon, B., Dubois, B. and Agid, Y., The mental representation of hand movements after parietal cortex damage. Science, 1996, 273, 1564-1567.] using their dominant and non-dominant hands. Analysis of group data indicated that both real and imagined movement conformed to Fitts' law. Analysis of individual data indicated that asymmetries arising from motor dominance in real movements also occurred for imagined movements. However, the relative slowing and error associated with the non-dominant hand was greater for imagined movements than for real movements. These asymmetries support the hypothesis that real and imagined movements are represented within the same neurocognitive networks but suggest that asymmetries in performance related to handedness are greater for imagined movements. In addition, while the visually guided pointing task provides a useful test of the ability to make imagined movements, asymmetries in the speed and reliability of imagined performance are significantly greater than those for real performance.     

Input-output organization of the foot motor area in humans.

OBJECTIVE: A well-organized input-output relation similar to that of the monkey motor cortex has been demonstrated in the human hand motor area (Terao Y, Ugawa Y, Uesaka Y, Hanajima R, Gemba-Shimizu K, Ohki Y, Kanazawa I. Input-output organization in the hand area of the human motor cortex, Electroenceph clin Neurophysiol 1995;97:375-381). The aim of this study is to investigate the input-output organization of the human foot motor area. METHODS: We studied the effect of tactile stimuli given to the toe tip on the sizes of following responses; motor evoked potentials (MEPs) elicited by transcranial magnetic or electrical stimulation (TMS or TES) over the motor cortex and magnetic stimulation at the foramen magnum level. RESULTS: Air stimuli applied to the toe tip facilitated magnetically evoked MEPs of mainly the muscle attached to that toe, although a less prominent facilitation was also noted in muscles attached to the adjacent toes. Neither responses evoked by TES, nor those by stimulation at the foramen magnum level, were affected by air stimuli. These results suggest that the observed facilitatory effect occurs at the cortical level. CONCLUSION: A fairly well-organized input-output relation is present also in the foot motor area in humans, although the facilitatory effect is not so topographically restricted as is noted for the hand motor area.     

The subthalamic nucleus is one of multiple innervation sites for long-range corticofugal axons: a single-axon tracing study in the rat

The frontal cortex provides strong excitatory inputs to the subthalamic nucleus (STN), and these cortico-STN inputs play critical roles in the control of basal ganglia activity. It has been assumed from anatomical and physiological studies that STN is innervated mainly by collaterals of thick and fast conducting pyramidal tract axons originating from the frontal cortex deep layer V neurons, implying that STN directly receives efferent copies of motor commands. To more closely examine this assumption, we performed biotinylated dextran amine anterograde tracing studies in rats to examine the cortical layer of origin, the sizes of parent axons, and whether or not the cortical axons emit any other collaterals to brain areas other than STN. This study revealed that the cortico-STN projection is formed mostly by collaterals of a small fraction of small-to-medium-sized long-range corticofugal axons, which also emit collaterals that innervate multiple other brain sites including the striatum, associative thalamic nuclei, superior colliculus, zona incerta, pontine nucleus, multiple other brainstem areas, and the spinal cord. The results imply that some layer V neurons are involved in associative control of movement through multiple brain innervation sites and that the cortico-STN projection is one part of this multiple corticofugal system.