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Inhibitory gating (IG) is a basic central nervous system process for filtering repetitive sensory information. Although IG deficits coincide with cognitive and emotional dysfunction in a variety of neuropsychiatric disorders, limited research has been completed on the basic, functional nature of IG. Persistent IG occurs in rut prelimbic medial prefrontal cortex (mPFC), a crucial site for modulating emotional learning. To investigate the interaction of affect and IG, we recorded local field potentials (LFP) directly from prelimbic mPFC and examined the influence of tone-shock fear conditioning (FC) on IG. Behavioral reactions during IG were observed before and after FC, and increase of orienting response after FC indicated induction of tone-shock association. After FC, some components of LFP response exhibited short-term weakening of IG. On a subsequent day of recording, IG strengthened for all LFP components, but individual components differed in their particular changes. Affective regulation of IG represents an important factor influencing within-subject IG variability, and these results have implications for understanding the role of rapid, implicit neural coding involved in emotional learning and affective disruption in psychiatric disease. Keywords: evoked potentials, prefrontal cortex, sensory gating, negative affect, acute stress

This study examined the relationship between sensorimotor and motivational functions of the corpus striatum. In rats, excitotoxic lesions of the corpus striatum (neostriatum and globus pallidus) caused by kainic or quisqualic acid can produce both aversive aphagia and a 'choreic' sensorimotor syndrome: an exaggerated treading of the forepaws that is triggered by oral sensory stimulation. Experiment 1 used a recovery-of-function approach to show that (a) aphagia induced by ventroposterior striatopallidal lesions was accompanied by an enhancement of aversion (a specific motivational process) to sweet stimuli, which was expressed in taste reactivity measures of affective evaluation; (b) aphagia and enhanced aversion recovered together; and (c) exaggerated treading did not disappear with aphagia-aversion but narrowed the range of its eliciting trigger to sour and bitter stimuli. Experiment 2 used a partial lesion approach to show that this dissociation of enhanced aversion and exaggerated treading could be reproduced by smaller lesions immediately after striatopallidal damage. Experiment 3 used a conditioned aversion procedure to show that the stimulus for exaggerated treading was aversion (natural or conditioned) and not a simple sensory feature of oral stimulation. Three conclusions were made: (a) Exaggerated treading after a small lesion or after partial recovery from a larger one results from a restructuring of a sensorimotor relations that is nested within a system of aversive reaction, (b) exaggerated treading is elicited only by tastes that elicit natural or conditioned aversion, and (c) more extensive lesions potentiate aversion to tastes that are normally palatable and expand the range of treading elicitors to include those tastes. In other words, affective and sensorimotor systems interact in a hierarchical manner in the production of choreic treading. These results demonstrate a specific hierarchical link between motivational and sensorimotor functions mediated by striatopallidal circuits.

Objective:Dopamine function is sensitive to toxin exposure. The environmental toxin polychlorinated biphenyl (PCB) alters dopamine physiology in several, harmful ways. Intermediary signals include thyroid hormones as PCB exposure alters thyroid function leading to changes in dopamine neurochemistry. To compare PCB and thyroid alterations directly, we exposed rats perinatally to either PCB (25 ppm) or thiouracil (THIO; 0.625%) from gestational day 1 to separation from the dam at postnatal day (PND) 25 and examined a set of tests sensitive to dopamine function.

Sensory gating (SG) is a prevalent physiological process important for information filtering in complex systems. SG is evaluated by presenting repetitious stimuli and measuring the degree of neural inhibition that occurs. SG has been found to be impaired in several psychiatric disorders. Recent animal and human research has made great progress in the study of SG, and in this review we provide an overview of recent research on SG using different methods. Animal research has uncovered findings that suggest 1) SG is displayed by single neurons and can be similar to SG observed from scalp recordings in humans, 2) SG is found in numerous brain structures located in sensory, motor and limbic subregions, 3) SG can be significantly influenced by state changes of the organism, and 4) SG has a diverse pharmacological profile accented by a strong influence from nicotine receptor activation. Human research has addressed similar issues using deep electrode recordings of brain structures. These experiments have revealed that 1) SG can be found in cortical regions surrounding hippocampus, 2) the order of neural processing places hippocampal involvement during a later stage of sensory processing than originally thought, and 3) multiple subtypes of gating exist that could be dependent on different brain circuits and more or less influenced by alterations in organismal state. Animal and human research both have limitations. We emphasize the need for integrative approaches to understand the process and combine information between basic and clinical fields so that a more complete picture of SG will emerge.

Background: Baclofen, a γ‐aminobutyric acid type B agonist, has been proposed as a pharmacotherapeutic agent in the treatment of addictive disorders such as alcoholism. Preclinical studies documenting the effect of baclofen on alcohol intake have provided conflicting results. The goal of this study was to determine the effect of baclofen pretreatment on ethanol‐ and sucrose‐reinforced responding.

This study investigated how different expected rewards influence behavior-related neuronal activity in the anterior striatum. In a spatial delayed-response task, monkeys reached for a left or right target and obtained a small quantity of one of two juices (apple, grenadine, orange, lemon, black currant, or raspberry). In each trial, an initial instruction picture indicated the behavioral target and predicted the reward. Nonmovement trials served as controls for movement relationships. Consistent preferences in special reward choice trials and differences in anticipatory licks, performance errors, and reaction times indicated that animals differentially expected the rewards predicted by the instructions. About 600 of >2,500 neurons in anterior parts of caudate nucleus, putamen, and ventral striatum showed five forms of task-related activations, comprising responses to instructions, spatial or nonspatial activations during the preparation or execution of the movement, and activations preceding or following the rewards. About one-third of the neurons showed different levels of task-related activity depending on which liquid reward was predicted at trial end. Activations were either higher or lower for rewards that were preferred by the animals as compared with nonpreferred rewards. These data suggest that the expectation of an upcoming liquid reward may influence a fraction of task-related neurons in the anterior striatum. Apparently the information about the expected reward is incorporated into the neuronal activity related to the behavioral reaction leading to the reward. The results of this study are in general agreement with an account of goal-directed behavior according to which the outcome should be represented already at the time at which the behavior toward the outcome is performed.

The neuroprotective effects of the NMDA antagonists MK-801 and ketamine were analyzed in a mutant strain of Han-Wistar rats which develop neurodegeneration in the hippocampus and cerebellum. Previous experiments have shown that the progressive neuronal degeneration observed in this mutant may be the result of a dysfunctional glutamatergic system. For MK-801 studies, mutants were injected in a chronic paradigm with (+)MK-801 or its weaker acting isomer (–)MK-801 at a dose of 1 mg/kg. Ketamine studies consisted of both acute (50 mg/kg once) and chronic (10 mg/kg multiple times) injection paradigms. MK-801-treated mutants exhibited longer life spans (8–23%) compared to saline-injected mutants. Ketamine-injected mutants in both paradigms also lived slightly longer (6–9%) than the saline mutants. Motor skill deterioration was monitored in an open-field test, and after 50 days of age the MK-801 and ketamine mutants displayed over 20% greater motor skill activity than the saline mutants. In the cerebellum, mutants treated with ketamine and both forms of MK-801 had 10–20% more Purkinje cells surviving at 55 days than the saline mutants. Further, the density of CA3c pyramidal hippocampal neurons in ketamine and MK-801-treated mutants as compared to saline mutants appeared to be greater upon qualitative analysis. This study shows that these mutants derive some protective effects from the NMDA antagonists MK-801 and ketamine, confirming glutamate-induced excitotoxicity as a possible cause of neuronal degeneration in this mutant strain of rat.

Systemic haloperidol injections decrease the severity of several hyperkinetic syndromes caused by damage to the basal ganglia in humans. A model of hyperkinesia in the rat, exaggerated paw treading triggered by oral sensory stimulation, has been reported previously to result from lesions of the globus pallidus or ventral pallidum/substantia innominata. This hyperkinesia appears as forepaw and forelimb extension and retraction, which can be emitted vigorously and repeatedly for up to minutes at a time. The present study aimed to discover whether this experimental hyperkinesia is pharmacologically similar to human hyperkinetic syndromes: can it be suppressed by neuroleptic administration? Systemic injections of haloperidol (2 mg/kg), diazepam (5 mg/kg, as a sedative comparison), or vehicle were given to rats that expressed the paw treading syndrome after pallidal lesions. Effects on hyperkinetic treading and on tests of sensorimotor function were compared. Results indicated that haloperidol was effective in ameliorating the hyperkinesia in rats with bilateral globus pallidus lesions but not in rats with ventral pallidum/substantia innominata lesions. By contrast, diazepam, which produced sedation and sensorimotor impairment, did not decrease the hyperkinesia induced by either lesion. Although only haloperidol decreased hyperkinetic treading after globus pallidus lesions, haloperidol produced less of a sensorimotor impairment than diazepam on climbing, hanging, and righting reflex tests. These results implicate a specific role for dopamine neurotransmission in the expression of triggered hyperkinetic treading induced by globus pallidus lesions.

Self-injurious behavior occurring in persons with severe mental retardation is a clinically significant and poorly understood problem. Multiple neurotransmitter systems have been implicated in the pathogenesis of this behavior, particularly dopaminergic, opioidergic, and serotonergic systems. Pemoline, a central stimulant, administered systemically at high doses reliably produces self-biting behavior in the rat. The systemic bolus of pemoline produces sustained neostriatal levels of pemoline for over 24 h in a continuous infusion paradigm. Studies of the effect of cortical lesions on pemoline-mediated behaviors reveal that cortical damage, as is common in profound mental retardation, lowers the threshold for pemoline-induced self-biting behavior. Data from the corticostriatal slice suggests that sustained exposure to pemoline produces a shift in N-methyl-D-aspartate receptor-mediated responses rendering them more susceptible to dopaminergic enhancement. Thus, dopaminergic and glutamatergic interactions appear to play an important role in the development and expression of self-biting in the pemoline model.