Cue-evoked dopamine release in the nucleus accumbens shell tracks reinforcer magnitude during intracranial self-stimulation.

The mesolimbic dopamine system is critically involved in modulating reward-seeking behavior and is transiently activated upon presentation of reward-predictive cues. It has previously been shown, using fast-scan cyclic voltammetry in behaving rats, that cues predicting a variety of reinforcers including food/water, cocaine or intracranial self-stimulation (ICSS) elicit time-locked transient fluctuations in dopamine concentration in the nucleus accumbens (NAc) shell. These dopamine transients have been found to correlate with reward-related learning and are believed to promote reward-seeking behavior. Here, we investigated the effects of varying reinforcer magnitude (intracranial stimulation parameters) on cue-evoked dopamine release in the NAc shell in rats performing ICSS. We found that the amplitude of cue-evoked dopamine is adaptable, tracks reinforcer magnitude and is significantly correlated with ICSS seeking behavior. Specifically, the concentration of cue-associated dopamine transients increased significantly with increasing reinforcer magnitude, while, at the same time, the latency to lever press decreased with reinforcer magnitude. These data support the proposed role of NAc dopamine in the facilitation of reward-seeking and provide unique insight into factors influencing the plasticity of dopaminergic signaling during behavior.

The basolateral amygdala differentially regulates conditioned neural responses within the nucleus accumbens core and shell.

The ability to process information regarding reward-predictive cues involves a diverse network of neural substrates. Given the importance of the nucleus accumbens (NAc) and the basolateral amygdala (BLA) in associative reward processes, recent research has examined the functional importance of BLA-NAc interactions. Here, multi-neuron extracellular recordings of NAc neurons coupled to microinfusion of GABAA and GABAB agonists into the BLA were employed to determine the functional contribution of the BLA to phasic neural activity across the NAc core and shell during a cued-instrumental task. NAc neural response profiles prior to BLA inactivation exhibited largely indistinguishable activity across the core and shell. However, for NAc neurons that displayed cue-related increases in firing rates during the task, BLA inactivation significantly reduced this activity selectively in the core (not shell). Additionally, phasic increases in firing rate in the core (not shell) immediately following the lever press response were also significantly reduced following BLA manipulation. Concurrent with these neural changes, BLA inactivation caused a significant increase in latency to respond for rewards and a decrease in the percentage of trials in which animals made a conditioned approach to the cue. Together, these results suggest that an excitatory projection from the BLA provides a selective contribution to conditioned neural excitations of NAc core neurons during a cued-instrumental task, providing insight into the underlying neural circuitry that mediates responding to reward-predictive cues.

In vivo voltammetric monitoring of catecholamine release in subterritories of the nucleus accumbens shell.

Fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes has been used to demonstrate that sub-second changes in catecholamine concentration occur within the nucleus accumbens (NAc) shell during motivated behaviors, and these fluctuations have been attributed to rapid dopamine signaling. However, FSCV cannot distinguish between dopamine and norepinephrine, and caudal regions of the NAc shell receive noradrenergic projections. Therefore, in the present study, we examined the degree to which norepinephrine contributes to catecholamine release within rostral and caudal portion of NAc shell. Analysis of tissue content revealed that dopamine was the major catecholamine detectable in the rostral NAc shell, whereas both dopamine and norepinephrine were found in the caudal subregion. To examine releasable catecholamines, electrical stimulation was used to evoke release in anesthetized rats with either stimulation of the medial forebrain bundle, a pathway containing both dopaminergic and noradrenergic projections to the NAc, or the ventral tegmental area/substantia nigra, the origin of dopaminergic projections. The catecholamines were distinguished by their responses to different pharmacological agents. The dopamine autoreceptor blocker, raclopride, as well as the monoamine and dopamine transporter blockers, cocaine and GBR 12909, increased evoked catecholamine overflow in both the rostral and caudal NAc shell. The norepinephrine autoreceptor blocker, yohimbine, and the norepinephrine transporter blocker, desipramine, increased catecholamine overflow in the caudal NAc shell without significant alteration of evoked responses in the rostral NAc shell. Thus, the neurochemical and pharmacological results show that norepinephrine signaling is restricted to caudal portions of the NAc shell. Following raclopride and cocaine or raclopride and GBR 12909, robust catecholamine transients were observed within the rostral shell but these were far less apparent in the caudal NAc shell, and they did not occur following yohimbine and desipramine. Taken together, the data demonstrate that catecholamine signals in the rostral NAc shell detected by FSCV are due to change in dopamine transmission.

Congenital cataract extraction with primary aphakia and secondary intraocular lens implantation in the posterior chamber.

PURPOSE: To evaluate visual outcomes, eye movement abnormalities, and postoperative complications after secondary posterior chamber intraocular lens (IOL) implantation in aphakic children who had initial LAC correction. METHODS: A retrospective study was carried out on 53 patients (94 eyes). Following aphakic surgery and LAC correction the patients received secondary IOL implantation in the posterior chamber. Special attention was paid to factors that may have influenced their visual outcomes, such as eye movement abnormalities, cataract unilaterality, and cataract density. RESULTS: No association was found between age at surgery and the onset of strabismus (p=0.611) or with visual acuity (p=0.086). However, unilaterality and total cataract density were found to have a negative association with poor vision (p<0.001). Strabismus and nystagmus were found to have a statistically significant negative association with visual acuity (p=0.002). Posterior capsule opacification occurred in six eyes of five patients following cataract extraction; IOL dislocation occurred in four eyes after IOL intraocular implantation, and secondary glaucoma occurred in one eye. CONCLUSIONS: IOL implantation before 12 months of age may be useful in unilateral cataract; in bilateral cataract, simultaneous surgical aphakia, LAC correction, and then IOL implantation at 2.5-3 years of age, together with anti-amblyopic therapy when strabismus or asymmetric cataract density occur, are efficient methods to obtain visual recovery. Extraocular muscle surgery may be required to correct strabismus.

Incidence of ocular pathologies in Italian children with Down syndrome.

PURPOSE: This study identifies the incidence of primary ocular pathologies in a population of Italian children with Down syndrome. METHODS: A total of 157 Italian children with Down syndrome, age between 1 month and 18 years, were screened between February 2005 and October 2006. The ophthalmologic evaluation included a global inspection of orbit and bulbus oculi, evaluation of ocular motility and visual acuity, slit lamp biomicroscopy, cycloplegic skiascopy, tonometry, and indirect ophthalmoscopy. RESULTS: The overall incidence of ocular abnormalities was epicanthal fold (132 patients, 84%), hyperopia (93 patients, 59%), astigmatism (44 patients, 28%), myopia (14 patients, 9%), strabismus (56 patients, 36%, 45 cases of esotropia and 11 cases of exotropia), congenital nasolacrimal duct obstruction (35 patients, 22%), cataract (18 patients, 11%), nystagmus (9 patients, 6%), blepharitis and conjunctivitis (6 patients, 4%), and retinal anomalies (10 patients, 6%). Unlike previous reports in patients with Down syndrome, no congenital glaucoma, keratoconus, or Brushfield spots were observed. CONCLUSIONS: Compared to other studies in patients with Down syndrome, we observed a higher incidence of hyperopia and a lower incidence of myopia. The incidence of nystagmus, blepharitis,and conjunctivitis was less than that reported in other studies, while strabismus, especially exotropia (20%), had a high incidence in our cohort. We also frequently observed obstruction of the nasolacrimal duct (22%), but no keratoconus or glaucoma.

Neural networks for advanced control of robot manipulators.

Presents an approach and a systematic design methodology to adaptive motion control based on neural networks (NNs) for high-performance robot manipulators, for which stability conditions and performance evaluation are given. The neurocontroller includes a linear combination of a set of off-line trained NNs, and an update law of the linear combination coefficients to adjust robot dynamics and payload uncertain parameters. A procedure is presented to select the learning conditions for each NN in the bank. The proposed scheme, based on fixed NNs, is computationally more efficient than the case of using the learning capabilities of the neural network to be adapted, as that used in feedback architectures that need to propagate back control errors through the model to adjust the neurocontroller. A practical stability result for the neurocontrol system is given. That is, we prove that the control error converges asymptotically to a neighborhood of zero, whose size is evaluated and depends on the approximation error of the NN bank and the design parameters of the controller. In addition, a robust adaptive controller to NN learning errors is proposed, using a sign or saturation switching function in the control law, which leads to global asymptotic stability and zero convergence of control errors. Simulation results showing the practical feasibility and performance of the proposed approach to robotics are given.

Selective activation of accumbens neurons by cocaine-associated stimuli during a water/cocaine multiple schedule.

Electrophysiological recording procedures were used to examine the responsiveness of nucleus accumbens (Acb) neurons to stimuli associated with cocaine delivery during a multiple schedule for water reinforcement and cocaine self-administration. Rats (n=9) were trained to press one lever for water reinforcement (0.05 ml/resp.; fixed ratio 1; FR1; 15 min) and a second spatially distinct lever for intravenous cocaine (0.33 mg/infusion; FR1; 2 h). The delivery of each reinforcer was signaled by different auditory stimuli. Of 101 neurons, 52 cells were classified as phasically active, exhibiting one of four well-defined types of patterned discharges relative to the water- or cocaine-reinforced response [J. Neurosci., 14(12) (1994) 7735; J. Neurosci., 20(11) (2000) 4255]. Acb cells were examined in test sessions consisting of 'probe' trials during which the stimulus previously paired with cocaine infusion was randomly presented in a response-independent manner during the self-administration portion of the session. Results showed that only neurons that exhibited changes in firing rate within seconds following the reinforced response for cocaine (but not water) were activated by the stimulus. This finding indicates that the responsiveness of cocaine selective neurons to cocaine-associated stimuli likely represents a conditioned response as opposed to a generalized stimulus-evoked discharge.

Heroin-induced suppression of saccharin intake in water-deprived and water-replete rats.

Rats suppress intake of a saccharin conditioned stimulus (CS) when paired with an aversive unconditioned stimulus such as lithium chloride. This phenomenon is referred to as a conditioned taste aversion (CTA). Rats also suppress intake of a saccharin CS when paired with a rewarding sucrose solution and when paired with a drug of abuse. Although the suppressive effects of drugs of abuse have long been interpreted as CTAs, evidence suggests that rats may suppress intake of the saccharin CS following taste-drug pairings because they are anticipating the rewarding rather than the aversive properties of the drug. Oddly, however, while all other drugs of abuse tested suppress intake of a gustatory CS, the highly reinforcing drug, heroin, is reportedly ineffective. The present study reexamined this issue in both water-deprived and water-replete rats using procedures that sustain both morphine- and cocaine-induced suppression of CS intake. The results showed that heroin greatly reduced CS intake following saccharin-heroin pairings and that this effect was less variable when assessed in water-replete subjects. When taken with other reports, these data suggest that rats suppress intake of a saccharin CS in anticipation of the availability of all drugs of abuse tested.

Nucleus accumbens cell firing during maintenance, extinction, and reinstatement of cocaine self-administration behavior in rats.

Electrophysiological recording procedures were used to examine nucleus accumbens (Acb) cell firing in rats (N=13) during cocaine self-administration sessions consisting of three phases. In phase one (maintenance), each lever press resulted in an intravenous cocaine infusion (0.33 mg, 6 s) paired with a tone-houselight stimulus (20 s). Of 144 Acb cells recorded during maintenance, 39 neurons (27%) exhibited phasic firing relative to the cocaine-reinforced response [4-8]. Briefly, Acb neurons showed increases in firing rate within seconds preceding the reinforced response and/or changes (increases or decreases) in activity within seconds following response completion. In phase two (extinction), saline was substituted for cocaine in the task. Results indicated that cells displaying exclusively anticipatory discharges during maintenance exhibited similar phasic activity during extinction. However, neurons that displayed post-response activity during the maintenance phase typically showed significant attenuation of phasic firing rates during extinction. After 30 min of no responding, animals were 'primed' with an intravenous infusion of cocaine, and self-administration was reestablished during phase three (reinstatement). Results showed that pre-response discharge patterns remained relatively intact while post-response cells typically exhibited a partial recovery of phasic activity. Similar findings were observed during other extinction experiments in which the stimulus only was removed (CS extinction). These findings support the notion that specific factors operating within the self-administration context differentially control pre- versus post-response discharge patterns of Acb neurons.

Evidence that separate neural circuits in the nucleus accumbens encode cocaine versus "natural" (water and food) reward.

Electrophysiological recording procedures were used to examine nucleus accumbens (Acb) cell firing in rats trained to press a lever on a multiple schedule [ fixed ratio (FR)1, FR1] for either two "natural" reinforcers (food and water), or a natural reinforcer and intravenous self-administration of cocaine. Of 180 cells recorded during water and food reinforcement (n = 13 rats), 77 neurons were classified as phasically active, exhibiting one of three well-defined types of patterned discharges relative to the reinforced-response (Carelli and Deadwyler, 1994). Of the 77 phasic cells, the majority (68%) showed similar types of patterned discharges across the two natural reinforcer conditions. In contrast, of 127 neurons recorded during water and cocaine reinforcement (n = 8 rats), only 5 of 60 phasically active cells (8%) exhibited similar types of patterned discharges relative to water- and cocaine-reinforced responding. The remaining 55 phasic cells (92%) displayed patterned discharges relative to the cocaine-reinforced response (n = 26 cells), or relative to the water-reinforced response (n = 29 cells), but not both. For some rats (n = 3), food was substituted for water in the task. Again, the majority of phasic neurons (13 of 14 cells, 93%) exhibited nonoverlapping firing patterns across the drug and natural reinforcer conditions. These findings indicate that in the well-trained animal, cocaine activates a neural circuit in the Acb that is largely separate from the circuit that processes information about food and water reward.

Activation of accumbens cell firing by stimuli associated with cocaine delivery during self-administration.

Electrophysiological recording procedures were used in behaving rats (n = 11) to examine the responsiveness of nucleus accumbens (Acb) neurons to stimuli associated with intravenous cocaine delivery during self-administration sessions. Of 208 Acb neurons recorded during cocaine (0.33 mg/inf) self-administration sessions, 78 cells exhibited one of four types of patterned discharges (increases and/or decreases in firing rate) immediately before and/or following the cocaine-reinforced response. All phasically active Acb cells were examined in test sessions consisting of "probe" trials (18-20 per session) during which either the drug only was delivered (0.33 mg/inf cocaine, 6 sec) or the stimulus only (tone-houselight, 20 sec) was randomly presented by the computer, interspersed between reinforced lever press responses. Results show that Acb cells that exhibit postresponse changes in firing rate within seconds of the reinforced response appear to be controlled, at least in part, by the stimulus paired with cocaine delivery during the self-administration session and not via a direct pharmacological action of cocaine. In contrast, neurons displaying exclusively preresponse activity do not appear to be influenced by presentation of the drug-associated stimulus or by a direct pharmacological action of the cocaine, but may be related to initiation of the operant response. These findings are discussed with respect to the role of the Acb in mediating conditioned responses associated with drug reinforcement.

Examination of factors mediating the transition to behaviorally correlated nucleus accumbens cell firing during cocaine self-administration sessions in rats.

We have previously reported that at the initiation of cocaine self-administration sessions, neurons in the nucleus accumbens (NA) exhibit a spontaneous transition in firing rate from activity unrelated to the reinforced response, to one of four types of patterned discharges (Carelli RM, King VC, Hampson RE, Deadwyler SA. Firing patterns of nucleus accumbens neurons during cocaine self-administration in rats. Brain Res 1993;626:14-22; Carelli RM, Deadwyler SA. Dose-dependent transitions in nucleus accumbens cell firing and behavioral responding during cocaine self-administration sessions in rats. J Pharm Exp Ther 1996;277(1):385 393; Carelli RM, Deadwyler SA. Cellular mechanisms underlying reinforcement-related processing in the nucleus accumbens: electrophysiological studies in behaving animals. Pharmacol Biochem Behav 1997;57:(2)1-10). This transition in NA cell firing is cocaine dose-dependent and is accompanied by a shift from high response rates at the start of the session ('Load-up' behavior) to a lower steady rate of responding thereafter (termed 'Session' phase responding). Two experiments were conducted to examine further factors that may mediate this process. Experiment 1 examined the effects of pre-session, response-independent delivery of cocaine on behavioral/neural transitions. Results revealed an absence of Load-up responding and the immediate onset of NA patterned activity at the start of the session. Experiment 2 examined the involvement of dopamine D1 versus D2 receptors in mediating the corresponding behavioral/neural transitions. Animals were pretreated with either saline, the dopamine D1 receptor antagonist SCH23390 (2.5-20 microg/kg, s.c.), or the dopamine D2 receptor antagonist eticlopride (2.5-20 microg/kg, s.c.) 30 min prior to the cocaine (0.33 mg/inf) self-administration session. SCH23390 significantly increased the number of Load-up responses at 10 and 20 microg/kg and the number of responses following the Load-up phase (i.e. during the Session phase) at 5, 10, and 20 microg/kg. Eticlopride increased the number of Session responses (5, 10, and 20 microg/kg), but did not alter the number of Load-up responses at any dose tested. The transition in NA cell firing corresponded with the shift in behavioral responding and was delayed within the session following SCH23390 but not eticlopride pretreatment. These findings support the notion that cocaine self-administration sessions in rats consists of two distinct behavioral phases that are mediated by different neurophysiological mechanisms operating in the NA.

Cellular mechanisms underlying reinforcement-related processing in the nucleus accumbens: electrophysiological studies in behaving animals.

Numerous investigations have implicated the nucleus accumbens (NA) as an important neural substrate involved in mediating reinforcement-related processing. Electrophysiological studies in behaving animals enable a direct examination of cellular mechanisms underlying this process via characterization of NA activity at critical times during responding for food, water, or drug reward. Electrophysiological studies are reported that examined the activity of NA neurons during water- and cocaine-reinforced responding in rats. These studies reveal that some NA neurons exhibit changes (increases or decreases) in firing rate synchronized to the response-contingent delivery of water or cocaine. Furthermore, the sampled population of NA neurons exhibited less synchronized cell firing during the response for cocaine than for the water reward. NA activity during cocaine self-administration was explicitly coupled to the behavioral state of the animal and was markedly influenced by the stimulus context in which the drug was delivered. These findings are discussed with respect to the dynamic properties of NA activity and its importance as an underlying cellular substrate mediating reinforcement-related events in the behaving animal.

Loss of lever press-related firing of rat striatal forelimb neurons after repeated sessions in a lever pressing task.

Lateral striatal neurons that fire phasically in relation to active movement of the contralateral forelimb (determined via daily sensorimotor examination) were studied during acquisition of cued lever pressing. Rats were trained to lift the contralateral forepaw from the floor to press a lever in the presence of a tone. The tone was presented 70 times per day (session) for 18 consecutive days. All animals acquired the task, evidenced by gradual improvements across sessions and eventual asymptotic levels in tone discrimination, reaction time, and efficiency of the lever press. Forelimb neurons fired in relation to the lever press during early sessions of acquisition but not after repeated sessions on the task. This difference in firing could not be attributed to differences in forelimb movements during lever pressing or to sampling from different populations of neurons in early versus late sessions. In view of evidence that striatal damage impairs acquisition of motor skills, the change in firing suggests that the striatal activity present in early sessions may be necessary for the acquisition of, but not the automatic performance of, learned motor responses.

Dose-dependent transitions in nucleus accumbens cell firing and behavioral responding during cocaine self-administration sessions in rats.

At the initiation of cocaine self-administration sessions, neurons in the rat nucleus accumbens (NA) exhibit a spontaneous transition in firing rate from activity unrelated to the reinforced response to one of four types of patterned discharges. This transition in NA activity is accompanied by a shift from high response rates at the start of the session ("Load-Up" behavior) to a lower rate for the remainder of the session. In this study, the relationship between transitions in behavioral responding and NA activity was examined further by changing the dose of cocaine per session (0.66, 0.50, 0.33, 0.16 or 0.08 mg/inf). Results show that the number of Load-Up responses significantly increased at lower cocaine doses [0.16, 0.08 mg/infusion (inf)] and decreased at higher doses (0.33, 0.50, 0.66 mg/inf). Thereafter, animals responded either with regularly spaced interinfusion intervals (INTs) at high doses (0.33, 0.50 and 0.66 mg/inf), or frequent bursts and pauses in responding at low doses (0.16 and 0.08 mg/inf. NA neurons exhibited a spontaneous transition in firing rate that was significantly correlated with this shift in behavioral responding across different doses of cocaine. Pretreatment with the dopamine D1 receptor antagonist SCH23390 (5 or 10 microgram/kg) prolonged the onset of NA patterned discharges, similar to responding for low doses of cocaine (0.08 and 0.16 mg/inf. These findings are discussed in terms of a functional role of the NA in mediating the reinforcing properties of cocaine.

A comparison of nucleus accumbens neuronal firing patterns during cocaine self-administration and water reinforcement in rats.

The firing patterns of nucleus accumbens (NA) neurons in the rat were recorded during cocaine self-administration and responding for water. Recordings were obtained from permanently implanted multiple-electrode arrays (eight microwires) inserted bilaterally into rostral portions of the NA in subjects (n = 18) exhibiting stable cocaine self-administration (0.33 mg/infusion), and during stable responding for water reinforcement. Electronically isolated and identified NA neurons exhibited four distinct patterns of phasic activity relative to the reinforced response. Three of these firing patterns were observed during both cocaine self-administration and water reinforcement sessions. Response-related activity was categorized by cells that showed an anticipatory increase in firing rate during the preresponse phase (type PR), and by cells that were excited (type RFE) or inhibited (type RFI) following the response in the reinforcement phase. PR and RFE cells showed significantly reduced peak firing during cocaine self-administration, compared to similar cells in water reinforcement sessions. A fourth type of NA firing pattern (type PR+RF) was observed only in cells recorded during cocaine self-administration sessions (Carelli et al., 1993b). PR+RF neurons exhibited two distinct peaks, one preceding the response and terminating at response completion (like PR cells), and a second peak immediately following the response (like RFE cells) with an inhibitory period between the two peaks (like RFI cells). The findings are discussed in terms of the role of the NA in mediating the reinforcing properties of both cocaine and water.

Firing patterns of nucleus accumbens neurons during cocaine self-administration in rats.

The firing patterns of neurons in the nucleus accumbens (NA) were recorded in rats trained to self-administer cocaine via response contingent intravenous drug infusions. Recordings were obtained from permanently implanted multiple electrode arrays (8 microwires) inserted bilaterally into the NA and/or ventral striatum (NA-VS) in animals exhibiting stable responding (inter-infusion intervals, INT) during test sessions consisting of 16-30 drug delivery episodes. Electronically isolated and identified NA-VS neurons showed distinct patterns of phasic increases in firing relative to the occurrence of the reinforced lever press. Two particular firing patterns, however, were repeatedly encountered in different animals. In one type, a marked increase was observed in discharge following response contingent drug delivery. A second firing pattern showed two distinct temporally separated brief firing peaks (bursts), one immediately prior to the initiation of responding, and the other a brief discharge commencing within 200 ms after the initiation of drug delivery. The time between firing peaks was found to be modifiable by changing the response/reward (FR) ratio for drug delivery. A third finding was that the correlates of the self-administration response were not solely the result of drug infusion since, (1) phasic firing increases were not observed when the drug was delivered non-contingently during the same session and, (2) the emergence of patterns was frequently delayed within the session until after drug self-administration behavior stabilized at regular INTs. The findings are discussed in terms of the significance of NA-VS neuron firing correlates for the initiation and maintenance of cocaine self-administration.

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)

A region in the dorsolateral striatum of the rat exhibiting single-unit correlations with specific locomotor limb movements.

1. To examine the activity of single units in the lateral striatum of the awake rat with respect to sensorimotor function, 788 units were recorded during locomotion and passive testing. The focus of this report is on 138 units (18%) that fired in relation to sensorimotor activity of a single limb. The remaining units were related to other body parts (16%), to general body movement (38%), or were unresponsive (28%). 2. Firing rates of limb-related units were near zero during resting behavior but increased markedly during treadmill locomotion. Each of the 138 units exhibited a rhythmic pattern of discharge in phase with the locomotor step cycle. Passive testing revealed that 86/97 units tested (89%) responded to passive manipulation of a single limb, exhibiting increased firing rates. Of these, 77 (90%) were related to contralateral and 9 (10%) to ipsilateral limbs. Sixty-one units (71%) were related to a forelimb and 25 (29%) to a hindlimb. Of the 86 units responding to passive manipulation. 34/48 units tested (71%) also responded to cutaneous stimulation of the same limb but no other part of the body. 3. To study in greater detail the rhythmic unit discharges in phase with the locomotor step cycle, computer-synchronized videotape recordings were used to generate perimovement time histograms constructed around discrete locomotor movements of each limb (n = 17 units). Activity of each unit was shown to be restricted to a specific portion of a particular limb's step cycle. The majority of units discharged throughout (8 units) or during a portion of (3 units) the swing phase, whereas other units fired during a portion of stance (3 units), footfall (2 units), or foot off (1 unit). 1. The specificity of unit firing was further demonstrated by the finding that rhythmic discharges, related to discrete locomotor limb movements in the forward direction, were completely absent during spontaneous deviations such as backward or disrupted locomotion. 5. Units related to limb movement were located in the far lateral, especially the dorsolateral, subregion of the striatum. This subregion extend rostrocaudally from A-P +1.6 to -1.0 mm relative to bregma. No clear somatotopic organization was observed, but this issue requires further study. 6. These results show that functional representations of individual limbs can be demonstrated in the lateral striatum of the rat, within a subregion containing terminals of projections from somatic sensorimotor cortex.(ABSTRACT TRUNCATED AT 400 WORDS)