Three-dimensional topography of corticopontine projections from rat sensorimotor cortex: comparisons with corticostriatal projections reveal diverse integrative organization

The major cortical-subcortical re-entrant pathways through the basal ganglia and cerebellum are considered to represent anatomically segregated channels for information originating in different cortical areas. A capacity for integrating unique combinations of cortical inputs has been well documented in the basal ganglia circuits but is largely undefined in the precerebellar circuits. To compare and quantify the amount of overlap that occurs in the first link of the cortico-ponto-cerebellar pathway, a dual tracing approach was used to map the spatial relationship between projections originating from the primary somatosensory cortex (SI), the secondary somatosensory cortex (SII), and the primary motor cortex (MI). The anterograde tracers biotinylated dextran amine and Fluoro-Ruby were injected into homologous whisker representations of either SI and SII, or SI and MI. The ensuing pontine labeling patterns were analyzed using a computerized three-dimensional reconstruction approach. The results demonstrate that whisker-related projections from SI and MI are largely segregated. At some locations, the two projections are adjoining and partly overlapping. Furthermore, SI contributes significantly more corticopontine projections than MI. By comparison, projections from corresponding representations in SI and SII terminate in similar parts of the pontine nuclei and display considerable amounts of spatial overlap. Finally, comparison of corticopontine and corticostriatal projections in the same experimental animals reveals that SI-SII overlap is significantly larger in the pontine nuclei than in the neostriatum. These structural differences indicate a larger capacity for integration of information within the same sensory modality in the pontocerebellar system compared to the basal ganglia.     

Representation of the body by single neurons in the dorsolateral striatum of the awake, unrestrained rat

Single cell recordings in awake monkeys and cats have demonstrated that individual body parts are represented within striatal subregions receiving projections from somatic sensorimotor cortex. Literature indicating that the lateral striatum of the rat receives similar cortical inputs and subserves sensorimotor functions prompted a study of whether this subregion contains similar representations of the body. Single cell recordings were obtained from 923 neurons of 24 awake, unrestrained rats. Of 788 neurons categorized according to body part, 264 (34%) discharged in relation to active movement, passive manipulation, and/or cutaneous stimulation of a particular part of the body; the remainder were related to global, whole body movement (38%) or were unresponsive (28%). Neurons related to individual body parts were recorded throughout the entire anterior-posterior extent of the dorsolateral striatum (+1.60 to -2.12 mm A-P, from bregma), intermingled among each other in all 3 dimensions. Two topographic arrangements were observed. First, neurons that fired rhythmically, in phase with low frequency (5-6 Hz) whisking of the vibrissae were segregated in the caudal striatum (-0.2 to -2.12 mm A-P) from neurons related to other body parts, which were distributed from +1.6 to -0.8 mm A-P. Second, representations of the head and face were located ventral to those of the limbs, despite substantial overlap in their overall distributions. A prominent feature of individual electrode tracks was the clustering together of cells related to the same body part. Neurons related to body parts exhibited substantial diversity, which took several distinct forms. Some neurons fired during movement or sensory stimulation in any direction, whereas others showed selectivity for a particular direction. Certain neurons responded to sensory stimulation of a large unilateral region of the body (e.g., all vibrissae or the entire forelimb), whereas others responded to stimulation of highly restricted regions (e.g., a single vibrissa or a single forepaw digit). Finally, neurons differed in the extent to which they exhibited active and passive properties. Among vibrissae-related neurons, one group fired rhythmically during whisking but did not respond to sensory stimulation of the vibrissae; a second group responded to sensory stimulation of the vibrissae but did not fire rhythmically during whisking; a third group showed both properties. Among limb-related neurons, firing during active movement was a property of every cell; none showed sensory responsiveness without showing a relation to active movement of one limb. Of the limb-related neurons, 89% tested responded to passive manipulation of the limb to which the neuron was actively related, and 71% also responded to cutaneous stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Neuronal activity in the medial associative‐limbic and lateral motor part of the rat subthalamic nucleus and the effect of 6‐hydroxydopamine‐induced lesions of the dorsolateral striatum

Lesions of the rat nigrostriatal dopamine system by injection of 6‐hydroxydopamine (6‐OHDA) lead to abnormal neuronal activity in the basal ganglia (BG) motor loop similar to that found in Parkinson's disease (PD). In the BG motor loop the subthalamic nucleus (STN) represents an important structure, which, however, also comprises areas of the BG associative and limbic loops. We were interested whether neuronal activity would differ between the STN medial associative‐limbic and lateral motor part, and whether selective 6‐OHDA‐induced lesions of the dorsolateral striatum, the entrance region of the BG motor loop, would differently affect these subregions. In male Sprague–Dawley rats 6‐OHDA (n = 12) or vehicle (n = 10) was bilaterally injected in the dorsolateral striatum. Four weeks later extracellular single‐unit activity and local field potentials were recorded in medial and lateral STN neurons of urethane‐anesthetized rats. In sham‐lesioned rats the discharge rate and burst activity were higher in the lateral compared to the medial STN. Similar differences were found for other neuronal activity measures (coefficient of variation of interspike interval, skewness, kurtosis, approximate entropy). After 6‐OHDA injection neuronal burst activity was enhanced, while the discharge rate was not affected. In addition, in 6‐OHDA‐lesioned rats β‐band oscillatory activity was enhanced, with no difference between STN subregions. We found important differences of neuronal activity between STN subregions, indicating functional segregation. However, selective 6‐OHDA lesions of the dorsolateral striatum also had a pronounced effect on the medial STN subregion, indicating interaction between BG loops. J. Comp. Neurol. 521:3226–3240, 2013. © 2013 Wiley Periodicals, Inc.     

Premovement activities in the subthalamic area of patients with Parkinson's disease and their dependence on task

Movement preparation and execution are associated with a reduction in oscillatory synchrony over 6-35 Hz (event-related desynchronization; ERD) and increases in oscillatory synchrony at higher frequencies (event-related synchronization; ERS) in the human parkinsonian subthalamic nucleus (STN). The timing of the ERD < 35 Hz in STN correlates with, but precedes, the timing of voluntary movement, in line with a role in motor processing. Here, we explore how directly the synchrony manifest in local field potential (LFP) activities depends on the details of motor processing. To this end, we recorded local field potentials from the STN area of parkinsonian subjects while they performed internally paced single movements or double movements with one hand. Analysis was limited to time periods that were unequivocally premovement, so as to avoid the confounding effects of sensory afferance during movement. LFP power differed from baseline activity as early as 2.1-1.1 s prior to movement over 6-18 Hz and 56-70 Hz. However, only the early changes in LFP power in the 56-70 Hz band depended on task type. Later on, within 0.5 s of the forthcoming movement, the behaviour of both the 6-18 and 56-70 Hz bands differed according to movement type. In addition, a change was seen in LFP activity over 23-35 Hz, although the ERD in this band remained similar across movement types. The findings further implicate the human STN in the feedforward organization of movement in premotor circuits. Different aspects of this organization may be preferentially reflected in changes in synchrony at different frequencies.     

The subthalamic region is activated during valence-related emotional processing in patients with Parkinson's disease

Visual stimuli are judged for their emotional significance based on two fundamental dimensions, valence and arousal, and may lead to changes in neural and body functions like attention, affect, memory and heart rate. Alterations in behaviour and mood have been encountered in patients with Parkinson's disease (PD) undergoing functional neurosurgery, suggesting that electrical high-frequency stimulation of the subthalamic nucleus (STN) may interfere with emotional information processing. Here, we use the opportunity to directly record neuronal activity from the STN macroelectrodes in patients with PD during presentation of emotionally laden and neutral pictures taken from the International Affective Picture System (IAPS) to further elucidate the role of the STN in emotional processing. We found a significant event-related desynchronization of STN alpha activity with pleasant stimuli that correlated with the individual valence rating of the pictures. Our findings suggest involvement of the human STN in valence-related emotional information processing that can potentially be altered during high-frequency stimulation of the STN in PD leading to behavioural complications.     

Alertness opens the effective flow of sensory information through rat thalamic posterior nucleus

Behavioural reactions to sensory stimuli vary with the level of arousal, but little is known about the underlying reorganization of neuronal networks. In this study, we use chronic recordings from the somatosensory regions of the thalamus and cortex of behaving rats together with a novel analysis of functional connectivity to show that during low arousal tactile signals are transmitted via the ventral posteromedial thalamic nucleus (VPM), a first‐order thalamic relay, to the primary somatosensory (barrel) cortex and then from the cortex to the posterior medial thalamic nucleus (PoM), which plays a role of a higher‐order thalamic relay. By contrast, during high arousal this network scheme is modified and both VPM and PoM transmit peripheral input to the barrel cortex acting as first‐order relays. We also show that in urethane anaesthesia PoM is largely excluded from the thalamo‐cortical loop. We thus demonstrate a way in which the thalamo‐cortical system, despite its fixed anatomy, is capable of dynamically reconfiguring the transmission route of a sensory signal in concert with the behavioural state of an animal.     

Effects of urethane anaesthesia on sensory processing in the rat barrel cortex revealed by combined optical imaging and electrophysiology

The spatiotemporal dynamics of neuronal assemblies evoked by sensory stimuli have not yet been fully characterised, especially the extent to which they are modulated by prevailing brain states. In order to examine this issue, we induced different levels of anaesthesia, distinguished by specific electroencephalographic indices, and compared somatosensory‐evoked potentials (SEPs) with voltage‐sensitive dye imaging (VSDI) responses in the rat barrel cortex evoked by whisker deflection. At deeper levels of anaesthesia, all responses were reduced in amplitude but, surprisingly, only VSDI responses exhibited prolonged activation resulting in a delayed return to baseline. Further analysis of the optical signal demonstrated that the reduction in response amplitude was constant across the area of activation, resulting in a global down‐scaling of the population response. The manner in which the optical signal relates to the various neuronal generators that produce the SEP signal is also discussed. These data provide information regarding the impact of anaesthetic agents on the brain, and show the value of combining spatial analyses from neuroimaging approaches with more traditional electrophysiological techniques.     

Morphology and synaptic connections of crossed corticostriatal neurons in the rat

The neurons of origin of the bilateral corticostriatal projection arising from the medial agranular cortical field in rats were identified by antidromic activation from contralateral neostriatal stimulation. The same cells were tested for antidromic activation from the contralateral neocortex and for orthodromic responses to stimulation of neocortex of the contralateral hemisphere or ipsilateral rostral thalamus. The neurons were then stained by intracellular injection of horseradish peroxidase. The laminar distribution of these neurons was compared to that of cortical cells stained retrogradely after injection of wheat germ agglutinin/HRP in the ipsilateral or contralateral neostriatum. The morphological features of physiologically identified corticostriatal neurons, their laminar organization, and their responses to stimulation were examined and compared with crossed corticocortical and brainstem-projecting cells. Crossed corticostriatal cells of the medial agranular cortical field were medium-sized pyramidal neurons found in the superficial part of layer V and in the deep part of layer III. Their basilar dendritic fields and initial intracortical axon collateral arborizations were coextensive with the layer defined by the distribution of corticostriatal neurons. The apical dendrites were thin and sparsely branched but consistently reached layer I, where they made a small arborization. These morphological features were shared by cortical neurons projecting to contralateral neocortex but not responding antidromically to stimulation of contralateral neostriatum, but they were not shared by brainstem-projecting cortical cells. Orthodromic responses to contralateral cortical stimulation consisted of brief excitatory postsynaptic potentials that were followed by powerful and longer-lasting inhibitory postsynaptic potentials. Corticostriatal cells also exhibited small excitatory postsynaptic potentials in response to thalamic stimulation. Many crossed corticostriatal neurons were also commissural corticocortical neurons. The results of reciprocal collision tests showed that this was due to the existence of two separate axonal branches, one projecting to contralateral neocortex and one to contralateral neostriatum. Intracellular staining of these neurons revealed ipsilateral axonal projections to the neostriatum and cortex.     

Synapse replacement in the striatum of the adult rat following unilateral cortex ablation

Defining the selective pattern of synapse replacement that occurs in different areas of the damaged brain is essential for predicting the limits of functional compensation that can be achieved after various types of brain injury. Here we describe the time course of dendritic reorganization, spine loss and recovery, and synapse replacement in the striatum following a unilateral cortex ablation. We found that the time course for the transient loss and recovery of dendritic spines on medium spiny I (MSI) neurons, the primary postsynaptic target for corticostriatal axons, paralleled the time course for the removal of degenerating axon terminals from the neuropil and the formation of new synapses on MSI neurons. Reinnervation of the deafferented striatum occurred chiefly by axon terminals that formed asymmetric synapses with dendritic spines of MSI neurons, and the mean density of asymmetric synapses recovered to 86% of the sham-operated rat value by 30 days postlesion. In addition, the synaptic circuitry of the reconstructed striatum was characterized by an increase in the number of multiple synaptic boutons (MSBs), i.e., presynaptic axon terminals that make contact with more than one dendritic spine. Whether the postsynaptic contacts of MSBs are formed with the dendritic spines of the same or a different parent dendrite in the striatum is unknown. Nevertheless, these data suggest that the formation of MSBs is an essential part of the compensatory response to the loss of input from the ipsilateral cortex following the aspiration lesion and may serve to modulate activity-dependent adaptive changes in the reconstructed striatum that can lead to functional recovery.     

Role of the somatosensory system in primary dystonia.

The pathophysiology of dystonia is still not fully understood, but it is widely held that a dysfunction of the corticostriatal-thalamocortical motor circuits plays a major role in the pathophysiology of this syndrome. Although the most dramatic symptoms in dystonia seem to be motor in nature, marked somatosensory perceptual deficits are also present in this disease. In addition, several lines of evidence, including neurophysiological, neuroimaging and experimental findings, suggest that both motor and somatosensory functions may be defective in dystonia. Consequently, abnormal processing of the somatosensory input in the central nervous system may lead to inefficient sensorimotor integration, thus contributing substantially to the generation of dystonic movements. Whether somatosensory abnormalities are capable of triggering dystonia is an issue warranting further study. Although it seems unlikely that abnormal somatosensory input is the only drive to dystonia, it might be more correlated to the development of focal hand than generalized dystonia because local somesthetic factors are more selectively involved in the former than in the latter where, instead it seems to be a widespread deficit in processing sensory stimuli of different modality. Because basal ganglia and motor areas are heavily connected not only with somatosensory areas, but also with visual and acoustic areas, it is possible that abnormalities of other sensory modalities, such as visual and acoustic, may also be implicated in the pathophysiology of more severe forms of primary dystonia. Further studies have to be addressed to the assessment of the role of sensory modalities and their interaction on the pathophysiology of different forms of primary dystonia.     

Imaging neurovascular function and functional recovery after stroke in the rat striatum using forepaw stimulation

Negative functional magnetic resonance imaging (fMRI) response in the striatum has been observed in several studies during peripheral sensory stimulation, but its relationship between local field potential (LFP) remains to be elucidated. We performed cerebral blood volume (CBV) fMRI and LFP recordings in normal rats during graded noxious forepaw stimulation at nine stimulus pulse widths. Albeit high LFP–CBV correlation was found in the ipsilateral and contralateral sensory cortices (r=0.89 and 0.95, respectively), the striatal CBV responses were neither positively, nor negatively correlated with LFP (r=0.04), demonstrating that the negative striatal CBV response is not originated from net regional inhibition. To further identify whether this negative CBV response can serve as a marker for striatal functional recovery, two groups of rats (n=5 each) underwent 20- and 45-minute middle cerebral artery occlusion (MCAO) were studied. No CBV response was found in the ipsilateral striatum in both groups immediately after stroke. Improved striatal CBV response was observed on day 28 in the 20-minute MCAO group compared with the 45-minute MCAO group (P<0.05). This study shows that fMRI signals could differ significantly from LFP and that the observed negative CBV response has potential to serve as a marker for striatal functional integrity in rats.     

Activity-dependent regulation of glutamic acid decarboxylase in the rat barrel cortex: effects of neonatal versus adult sensory deprivation.

Immunocytochemical techniques were used to study the effects of tactual deprivation on glutamic acid decarboxylase (GAD) containing neurons in rat somatosensory barrel cortex. In normal rats GAD immunoreactive neurons and puncta are present in all laminae, with dense patches of GAD immunoreactive puncta centered on the barrels in lamina IV. Trimming whiskers of adult rats leads to a reversible decrease of GAD immunoreactivity in barrels corresponding to trimmed hairs. Intensity of GAD staining also is reversibly altered in supragranular laminae of nondeprived barrel columns flanked by deprived barrels. This indicates that GAD levels in the barrel cortex ordinarily fluctuate with changes in sensory input. By contrast, animals whose whiskers are trimmed from birth have normal GAD staining in both deprived and nondeprived barrels. Moreover, if trimmed whiskers of neonatally deprived animals are allowed to grow to normal lengths and are retrimmed later in adulthood GAD staining is not affected. Thus early tactual deprivation disrupts mechanisms that permit modulation of transmitter enzyme levels in cortical neurons following changes in sensory experience.     

Primary sensory and forebrain motor systems in the newborn brain are preferentially damaged by hypoxia-ischemia

Cerebral hypoxia-ischemia causes encephalopathy and neurologic disabilities in newborns by unclear mechanisms. We tested the hypothesis that hypoxia-ischemia causes brain damage in newborns that is system-preferential and related to regional oxidative metabolism. One-week-old piglets were subjected to 30 minutes of hypoxia and then seven minutes of airway occlusion, producing asphyxic cardiac arrest, followed by cardiopulmonary resuscitation and four-day recovery. Brain injury in hypoxic-ischemic piglets (n = 6) compared to controls (n = 5) was analyzed by hematoxylin-eosin, Nissl, and silver staining; relationships between regional vulnerability and oxidative metabolism were evaluated by cytochrome oxidase histochemistry. Profile counting-based estimates showed that 13% and 27% of neurons in layers II/III and layers IV/V of somatosensory cortex had ischemic cytopathology, respectively; CA1 neuronal perikarya appeared undamaged, and <10% of CA3 and CA4 neurons were injured; and neuronal damage was 79% in putamen, 17% in caudate, but nucleus accumbens was undamaged. Injury was found preferentially in primary sensory neocortices (particularly somatosensory cortex), basal ganglia (predominantly putamen, subthalamic nucleus, and substantia nigra reticulata), ventral thalamus, geniculate nuclei, and tectal nuclei. In sham piglets, vulnerable regions generally had higher cytochrome oxidase levels than less vulnerable areas. Postischemic alterations in cytochrome oxidase were regional and laminar, with reductions (31–66%) occurring in vulnerable regions and increases (20%) in less vulnerable areas. We conclude that neonatal hypoxia-ischemia causes highly organized, system-preferential and topographic encephalopathy, targeting regions that function in sensorimotor integration and movement control. This distribution of neonatal encephalopathy is dictated possibly by regional function, mitochondrial activity, and connectivity. J. Comp. Neurol. 377:262–285, 1997. © 1997 Wiley-Liss, Inc.     

Modulation of high-frequency (600 Hz) somatosensory-evoked potentials after rTMS of the primary sensory cortex

Somatosensory inputs to the primary sensory cortex (S1) after median nerve stimulation include temporally overlapping parallel processing, as reflected by standard low-frequency somatosensory-evoked potentials (LF-SEPs) and high-frequency SEPs (HF-SEPs), the latter being more sensitive to arousal and to other rapid adaptive changes. Experimental data suggest that cortical HF-SEPs are formed by two successive pre- and postsynaptic components, respectively, generated in the terminal part of thalamo-cortical radiation (early burst) and in specialized neuronal pools within S1 (later burst). In eight healthy subjects, slow (1 Hz) or rapid (10 Hz) repetitive transcranial magnetic stimulations (rTMS), which are known to induce opposite changes on cortical excitability, applied on S1 did not modify LF-SEPs, while HF-SEPs showed a series of dissociate changes in the early and later high-frequency burst, moreover occurring with a different time-course. Slow rTMS caused an immediate and lasting decrease of the later burst activity, coupled with an immediate increase of the earlier part of the burst, suggesting that inhibition of cortical excitability triggered opposite, compensatory effects at subcortical levels; rapid rTMS induced a delayed increase of later HF-SEPs, leaving unaltered the earlier subcortical burst. Findings causally demonstrate that LF- and HF-SEPs reflect two distinct functional pathways for somatosensory input processing, and that early and late high-frequency burst do actually reflect the activity of different generators, as suggested by experimental data. Possible underlying neurophysiological phenomena are discussed.     

Electrophysiological evidence of alterations to the nucleus accumbens and dorsolateral striatum during chronic cocaine self‐administration

As drug use becomes chronic, aberrant striatal processing contributes to the development of perseverative drug‐taking behaviors. Two particular portions of the striatum, the nucleus accumbens (NAc) and the dorsolateral striatum (DLS), are known to undergo neurobiological changes from acute to chronic drug use. However, little is known about the exact progression of changes in functional striatal processing as drug intake persists. We sampled single‐unit activity in the NAc and DLS throughout 24 daily sessions of chronic long‐access cocaine self‐administration, and longitudinally tracked firing rates (FR) specifically during the operant response, an upward vertical head movement. A total of 103 neurons were held longitudinally and immunohistochemically localised to either NAc Medial Shell (n = 29), NAc Core (n = 30), or DLS (n = 54). We modeled changes representative of each category as a whole. Results demonstrated that FRs of DLS Head Movement neurons were significantly increased relative to baseline during all sessions, while FRs of DLS Uncategorised neurons were significantly reduced relative to baseline during all sessions. NAc Shell neurons' FRs were also significantly decreased relative to baseline during all sessions while FRs of NAc Core neurons were reduced relative to baseline only during training days 1–18 but were not significantly reduced on the remaining sessions (19–24). The data suggest that all striatal subregions show changes in FR during the operant response relative to baseline, but longitudinal changes in response firing patterns were observed only in the NAc Core, suggesting that this region is particularly susceptible to plastic changes induced by abused drugs.     

The functional connectivity of intralaminar thalamic nuclei in the human basal ganglia

Projections of the centromedian‐parafasicularis neurons of the intralaminar thalamus are major inputs of the striatum. Their functional role in the activity of human basal ganglia (BG) is not well known. The aim of this work was to study the functional connectivity of intralaminar thalamic nuclei with other BG by using the correlations of the BOLD signal recorded during “resting” and a motor task. Intralaminar nuclei showed a marked functional connectivity with all the tested BG, which was observed during “resting” and did not change with the motor task. As regards the intralaminar nuclei, BG connectivity was much lower for the medial dorsal nucleus (a thalamic nucleus bordering the intralaminar nuclei) and for the default mode network (although intralaminar nuclei showed a negative correlation with the default mode network). After the “regression” of intralaminar nuclei activity (partial correlation), the functional connectivity of the caudate and putamen nuclei with other BG decreased (but not with the primary sensorimotor cortex). Present data provide evidence that intralaminar nuclei are not only critical for striatal activity but also for the global performance of human BG, an action involving subcortical BG loops more than cortico‐subcortical loops. The high correlation found between BG suggest that, similarly to that reported in other brain centers, the very‐slow frequency fluctuations are relevant for the functional activity of these centers. Hum Brain Mapp 36:1335–1347, 2015. © 2014 Wiley Periodicals, Inc .     

Subthalamic nucleus stimulation restores the efferent cortical drive to muscle in parallel to functional motor improvement

Pathological synchronization in large-scale motor networks constitutes a pathophysiological hallmark of Parkinson's disease (PD). Corticomuscular synchronization in PD is pronounced in lower frequency bands (< 10 Hz), whereas efficient cortical motor integration in healthy persons is driven in the beta frequency range. Electroencephalogram and electromyogram recordings at rest and during an isometric precision grip task were performed in four perioperative sessions in 10 patients with PD undergoing subthalamic nucleus deep-brain stimulation: (i) 1 day before (D0); (ii) 1 day after (D1); (iii) 8 days after implantation of macroelectrodes with stimulation off (D8StimOff); and (iv) on (D8StimOn). Analyses of coherence and phase delays were performed in order to challenge the effects of microlesion and stimulation on corticomuscular coherence (CMC). Additionally, local field potentials recorded from the subthalamic nucleus on D1 allowed comprehensive mapping of motor-related synchronization in subthalamocortical and cerebromuscular networks. Motor performance improved at D8StimOn compared with D0 and D8StimOff paralleled by a reduction of muscular activity and CMC in the theta band (3.9-7.8 Hz) and by an increase of CMC in the low-beta band (13.7-19.5 Hz). Efferent motor cortical drives to muscle presented mainly below 10 Hz on D8StimOff that were suppressed on D8StimOn and occurred on higher frequencies from 13 to 45 Hz. On D1, coherence of the high-beta band (20.5-30.2 Hz) increased during movement compared with rest in subthalamomuscular and corticomuscular projections, whereas it was attenuated in subcorticocortical projections. The present findings lend further support to the concept of pathological network synchronization in PD that is beneficially modulated by stimulation.     

Lesions of dorsolateral striatum preserve outcome expectancy but disrupt habit formation in instrumental learning

Habits are controlled by antecedent stimuli rather than by goal expectancy. Interval schedules of feedback have been shown to generate habits, as revealed by the insensitivity of behaviour acquired under this schedule to outcome devaluation treatments. Two experiments were conducted to assess the role of the dorsolateral striatum in habit learning. In Experiment 1, sham operated controls and rats with dorsolateral striatum lesions were trained to press a lever for sucrose under interval schedules. After training, the sucrose was devalued by inducing taste aversion to it using lithium chloride, whereas saline injections were given to the controls. Only rats given the devaluation treatment reduced their consumption of sucrose and this reduction was similar in both the sham and the lesioned groups. All rats were then returned to the instrumental chamber for an extinction test, in which the lever was extended but no sucrose was delivered. In contrast to sham operated controls, rats with dorsolateral striatum lesions refrained from pressing the lever if the outcome was devalued. To assess the specificity of the role of dorsolateral striatum in this effect a second experiment was conducted in which a group with lesions of dorsomedial striatum was added. In relation now to both the sham and the dorsomedial lesioned groups, only rats with lesions of dorsolateral striatum significantly reduced responding after outcome devaluation. In conclusion, this study provides direct evidence that the dorsolateral striatum is necessary for habit formation. Furthermore, it suggests that, when the habit system is disrupted, control over instrumental performance reverts to the system controlling the performance of goal-directed instrumental actions.     

Single-axon tracing study of corticostriatal projections arising from primary motor cortex in primates

The axonal projections arising from the forelimb area of the primary motor cortex (M1) in cynomolgus monkeys (Macaca fascicularis) were studied following microiontophoretic injections of biotinylated dextran amine under electrophysiological guidance. The microinjections were centered on layer V, and 42 anterogradely labeled corticofugal axons were reconstructed from serial frontal or sagittal sections with a camera lucida. Our investigation shows that the primate striatum receives both direct and indirect projections from M1. The direct corticostriatal projection is formed by axons that remain uniformly thin and unbranched throughout their sinuous trajectory to the ipsilateral striatum. They divide as they enter the dorsolateral sector of the post-commissural putamen, the so-called sensorimotor striatal territory. The indirect corticostriatal projection derives from a thin collateral emitted within the corona radiata by thick, long-range fibers that descend toward the brainstem. The collateral enters the putamen dorsomedially and remains unbranched until it reaches the dorsolateral sector of the putamen, where it breaks out into two to four axonal branches displaying small and equally spaced varicosities. Both direct and indirect corticostriatal axons branch moderately but occupy vast rostrocaudal striatal territories, where they appear to contact en passant several widely distributed striatal neurons. These findings reveal that, in contrast to current beliefs, the primate motor corticostriatal system is not exclusively formed by axons dedicated solely to the striatum. It also comprises collaterals from long-range corticofugal axons, which can thus provide to the striatum a copy of the neural information that is being conveyed to the brainstem and/or spinal cord.