Biomedical subjects

Jon C Horvitz

Publications and source records attributed to Jon C Horvitz.

8 recordsLinked to original sources

PubMed2006

Amphetamine affects the start of responding in the peak interval timing task.

In this paper we investigate how amphetamine affects performance in a PI task by comparing two analyses of responding during peak trials. After training on 24 s fixed interval (FI-24) with 96 s peak trials, rats were given amphetamine for 4 consecutive days at doses of .5 and 1.0 mg/kg. Responses during peak trials were fitted with a Gaussian distribution to estimate the expected time of reinforcement from the peak time. A single trials analysis was also performed to determine the start time and stop time of the transition into and out of a high rate of responding on each peak trial. Amphetamine significantly decreased peak times as measured with the Gaussian curve fitting. However, in the single trials analysis, animals initiated responding significantly earlier, but did not stop responding earlier. Thus, fitting a Gaussian to the average performance across trials sometimes provides a different characterization of the timing process than does analyzing the start and stop of responding on individual trials. In the current experiment, the latter approach provided a more precise characterization of the effects of amphetamine on response timing.

Amphetamine↗

PubMed2006

Visual search deficits in Parkinson's disease are attenuated by bottom-up target salience and top-down information.

Patients with Parkinson's disease (PD), a degenerative disorder primarily affecting the nigrostriatal dopamine system, exhibit deficits in selecting task-relevant stimuli in the presence of irrelevant stimuli, such as in visual search tasks. However, results from previous studies suggest that these deficits may vary as a function of whether selection must rely primarily on the "bottom-up" salience of the target relative to background stimuli, or whether "top-down" information about the identity of the target is available to bias selection. In the present study, moderate-to-severe medicated PD patients and age-matched controls were tested on six visual search tasks that systematically varied the relationship between bottom-up target salience (feature search, noisy feature search, conjunction search) and top-down target knowledge (Target Known versus Target Unknown). Comparison of slope and intercepts of the RT x set size function provided information about the efficiency of search and non-search (e.g., decision, response) components, respectively. Patients exhibited higher intercepts than controls as bottom-up target salience decreased, however these deficits were disproportionately larger under Target Unknown compared to Target Known conditions. Slope differences between PD and controls were limited to the Target Unknown Conjunction condition, where patients exhibited a shallower slope in the target absent condition, indicating that they terminated search earlier. These results suggest that under conditions of high background noise, medicated PD patients were primarily impaired in decision and/or response processes downstream from the target search itself, and that the deficit was attenuated when top-down information was available to guide selection of the target signal.

Aged↗

PubMed2006

Dopamine receptor blockade and extinction differentially affect behavioral variability.

Dopamine (DA) neurons respond to unexpected food delivery and are inhibited during the omission of expected reward. DA receptor blockade mimics some, but not all, aspects of non-reward (extinction) conditions. It was therefore of interest to ask whether DA receptor blockade produces extinction-like increases in behavioral variability in addition to its well-known operant response-suppressing effects. In the current experiment, rats were trained drug-free on an operant task in which they pressed on a keyboard. Two of the keys led to food on a continuous reinforcement schedule. Both response rates and behavioral variability were measured. Test day administration of D(1) and D(2) antagonists SCH23390 and raclopride, like extinction, suppressed responding but, unlike extinction, did not lead to an increase in variability.

Analysis of Variance↗

PubMed2005

Extended habit training reduces dopamine mediation of appetitive response expression.

A wide range of behaviors is impaired after disruption of dopamine (DA) transmission, yet behaviors that are reflexive, automatic, or elicited by salient cues often remain intact. Responses triggered by strong external cues appear to be DA independent. Here, we examined the possibility that a single behavior may become DA independent as a result of extended training. Rats were trained to execute a head-entry response to a cue signaling food delivery. Vulnerability of the response to D1 or D2 receptor blockade was assessed on day 3, 7, or 17 of 28-trial-per-day training. During the early stages of training, the D1 receptor antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH 23390) increased response latencies; however, the same behavior was unaffected by SCH 23390 in animals tested during the later stages of training. Other aspects of behavior such as locomotion and head-entry responses during the uncued intertrial interval remained vulnerable to SCH 23390 throughout the experiment. This D1-mediated response was unaffected by the D2 antagonist raclopride, even at a dose that strongly suppressed locomotion. The results provide strong evidence that a D1-dependent behavior becomes less dependent on DA with extended training. A number of fundamental neurobiological changes occur as behaviors become learned habits; at least for some responses, this change involves a shift from D1-mediated to D1-independent responding.

Animals↗

PubMed2005

Maintenance of response readiness in patients with Parkinson's disease: evidence from a simple reaction time task.

The authors explored the effect of Parkinson's disease (PD) on the generation and maintenance of response readiness in a simple reaction time task. They compared performance of idiopathic PD patients without dementia, age-matched controls, and younger controls over short (1-, 3-, and 6-s) and long (12- and 18-s) foreperiod intervals. After each trial, the authors probed memory for visual information that also had to be maintained during the trial interval. Patients and controls did not differ overall in their ability to maintain readiness over long delays. However, within the PD group only, errors in maintaining visual information were correlated with difficulty in maintaining readiness, suggesting that systems impaired in PD may facilitate the maintenance of processing in both motor and cognitive domains.

Adult↗

PubMed2003

Opposing roles of D1 and D2 receptors in appetitive conditioning.

Previous studies have shown that D(1) receptor blockade disrupts and D(2) receptor blockade enhances long-term potentiation. These data lead to the prediction that D(1) antagonists will attenuate and D(2) antagonists will potentiate at least some types of learning. The prediction is difficult to test, however, because disruptions in either D(1) or D(2) transmission lead to reduced locomotion, exploration, and response execution and are therefore likely to impair learning that requires behavioral responding (including exploration of an environment) during the learning episode. Under a paradigm that minimizes motor requirements, rats were trained to enter a food compartment during pellet presentation. Animals then received tone-food pairings under the influence of D(1) antagonist SCH23390 (0, 0.4, 0.8, and 0.16 mg/kg) or D(2) antagonist raclopride (0, 0.2, 0.4, and 0.8 mg/kg). An additional group received unpaired presentations of tone and food. On a drug-free test day 24 hr later, animals that had been under the influence of SCH23390 (like animals that had received unpaired presentations of tone and food) showed reduced head entries in response to the tone, whereas animals that had been under the influence of raclopride showed increased head entries in response to the tone compared with vehicle controls. These data demonstrate that, under a conditioned approach paradigm, D(1) and D(2) family receptor antagonists disrupt and promote learning, respectively, as predicted by the effects of D(1) and D(2) receptor blockade on neuronal plasticity.

Acoustic Stimulation↗

PubMed2003

Effects of dopamine antagonists on the timing of two intervals.

Rats were trained on a two-interval (12 and 36 s) temporal production task (the peak procedure). Test sessions were conducted in which either the D(1) antagonist SCH-23390 (SCH; 0.02, 0.04, 0.06 mg/kg) or the D(2) antagonist haloperidol (HAL; 0.05, 0.1, 0.2 mg/kg) were injected prior to testing. Both drugs affected the amount of responding, but only HAL affected timing. Under HAL, both intervals were overestimated, consistent with a HAL-induced decrease in clock speed. Drug-induced decreases in response output were more profound for the long interval than the short. In addition, there was evidence of HAL- and SCH-induced delays in response initiation that were more severe for the long interval, perhaps owing to its status as a weaker conditioned stimulus.

Acoustic Stimulation↗

PubMed2002

Dopamine gating of glutamatergic sensorimotor and incentive motivational input signals to the striatum.

Dopamine (DA) neurons of the substantia nigra (SN) and ventral tegmental area (VTA) respond to a wide category of salient stimuli. Activation of SN and VTA DA neurons, and consequent release of nigrostriatal and mesolimbic DA, modulates the processing of concurrent glutamate inputs to dorsal and ventral striatal target regions. According to the view described here, this occurs under conditions of unexpected environmental change regardless of whether that change is rewarding or aversive. Nigrostriatal and mesolimbic DA activity gates the input of sensory, motor, and incentive motivational (e.g. reward) signals to the striatum. In light of recent single-unit and brain imaging data, it is suggested that the striatal reward signals originate in the orbitofrontal cortex and basolateral amygdala (BLA), regions that project strongly to the striatum. A DA signal of salient unexpected event occurrence, from this framework, gates the throughput of the orbitofrontal glutamate reward input to the striatum just as it gates the throughput of corticostriatal sensory and motor signals needed for normal response execution. Processing of these incoming signals is enhanced when synaptic DA levels are high, because DA enhances the synaptic efficacy of strong concurrent glutamate inputs while reducing the efficacy of weak glutamate inputs. The impairments in motor performance and incentive motivational processes that follow from nigrostriatal and mesolimbic DA loss can be understood in terms of a single mechanism: abnormal processing of sensorimotor and incentive motivation-related glutamate input signals to the striatum.

Amygdala↗