Biomedical subjects

Yogita Chudasama

Publications and source records attributed to Yogita Chudasama.

8 recordsLinked to original sources

PubMed2005

Time-limited modulation of appetitive Pavlovian memory by D1 and NMDA receptors in the nucleus accumbens.

Recent research has implicated the nucleus accumbens (NAc) in consolidating recently acquired goal-directed appetitive memories, including spatial learning and other instrumental processes. However, an important but unresolved issue is whether this forebrain structure also contributes to the consolidation of fundamental forms of appetitive learning acquired by Pavlovian associative processes. In addition, although dopaminergic and glutamatergic influences in the NAc have been implicated in instrumental learning, it is unclear whether similar mechanisms operate during Pavlovian conditioning. To evaluate these issues, the effects of posttraining intra-NAc infusions of D1, D2, and NMDA receptor antagonists, as well as d-amphetamine, were determined on Pavlovian autoshaping in rats, which assesses learning by discriminated approach behavior to a visual conditioned stimulus predictive of food reward. Intracerebral infusions were given either immediately after each conditioning session to disrupt early memory consolidation or after a delay of 24 h. Findings indicate that immediate, but not delayed, infusions of both D1 (SCH 23390) and NMDA (AP-5) receptor antagonists significantly impair learning on this task. By contrast, amphetamine and the D2 receptor antagonist sulpiride were without significant effect. These findings provide the most direct demonstration to date that D1 and NMDA receptors in the NAc contribute to, and are necessary for, the early consolidation of appetitive Pavlovian learning.

Animals↗

PubMed2004

Cortical cholinergic function and deficits in visual attentional performance in rats following 192 IgG-saporin-induced lesions of the medial prefrontal cortex.

Lesions of the basal forebrain (BF) cortical cholinergic system impair performance on a rodent five-choice visual attentional task. This study examines the effects on the same task of selective depletion of acetylcholine from the prefrontal cortex (PFC) using 192 IgG-saporin, the cholinergic immunotoxin. Rats were trained to detect brief visual stimuli, either presented unpredictably both temporally and spatially to increase attentional load, or under less demanding conditions where stimuli were temporally and spatially predictable. Following training, 192 IgG-saporin (50 ng or 100 ng/infusion) or its vehicle was infused bilaterally into the ventromedial PFC. The 100 ng lesion group exhibited post-operatively a transient increase in perseveration, specifically when the visual stimuli were temporally unpredictable. A vigilance decrement, as well as a reinstatement of perseverative responding occurred in both lesion groups under conditions of enhanced attentional load, specifically with high target frequency sustained over many trials. Lesioned subjects were also more impulsive with increased anticipatory errors. Systemic administration of the muscarinic receptor antagonist scopolamine further dissociated the groups with attentional accuracy in the 100 ng group decreasing relative to shams. These findings are consistent with an important modulatory influence of PFC function by BF cholinergic neurons, particularly during increased attentional demand.

Acetylcholine↗

PubMed2004

Dopaminergic modulation of visual attention and working memory in the rodent prefrontal cortex.

Converging evidence suggests that dopaminergic projections to the prefrontal cortex (PFC) modulate both attention and working memory processes that may be related to either insufficient or excessive dopamine activity specific to a D1 receptor mechanism. We examined the effects of bilateral intraprefrontal cortical infusions of the D1 agonist (SKF 81297) on a novel task specifically designed to assess the animals' ability to attend to a visual target (0.7 or 0.5 s) and then remember the location of that target over a variable delay (0-16 s) within the same test session. Bilateral prefrontal infusions of the low dose of SKF 81297 (0.01 microg) had no effect on visual attention or memory throughout the entire testing schedule. The medium (0.06 microg) dose preferentially increased attention to the stimulus target but only improved memory for that stimulus at a duration of 0.7 s, although in a delay-independent manner. The high dose (0.3 microg) of the D1 agonist also increased attentional accuracy. However, it was only under the more attention challenging condition (0.5 s) that this high dose also produced a baseline delay-dependent modulation of memory for the stimulus target. Specifically, good memory at the short delay was impaired and poor memory at the long delay was improved. These data provide the first demonstration that dopamine D1 receptor stimulation sufficient to improve attentional accuracy, can also disrupt, and facilitate short-term working memory performance in a delay-dependent manner.

Animals↗

PubMed2003

Functional disconnection of the medial prefrontal cortex and subthalamic nucleus in attentional performance: evidence for corticosubthalamic interaction.

The present study used a disconnection procedure to test whether the medial prefrontal cortex (mPFC) and the subthalamic nucleus (STN) were functional components in a common neural system that controlled continuous performance in a test of sustained and divided visual attention. Animals with disconnected lesions of the mPFC and STN in contralateral hemispheres were severely impaired in several aspects of performance, including discriminative accuracy, increased perseveration, and slowed response latencies during postoperative testing. These deficits persisted throughout the entire experimental test period. Increasing the stimulus duration alleviated the accuracy deficit but failed to improve speed of responding or reduce perseverative responses. These deficits were in marked contrast to animals with combined mPFC and STN lesions made on the ipsilateral side, which produced behavior not different from that of sham controls. Rats with unilateral lesions of either structure alone were also impaired in terms of accuracy and perseveration. These data suggest that some of the deficits observed after bilateral STN lesions (attention and perseveration) may be attributable to a disrupted corticosubthalamic projection. This study provides direct evidence that performance in tasks that require optimal attentional and executive control relies on a corticosubthalamic interaction within the neural circuitry of the basal ganglia.

Animals↗

PubMed2003

Intra-prefrontal 8-OH-DPAT and M100907 improve visuospatial attention and decrease impulsivity on the five-choice serial reaction time task in rats.

RATIONALE: The central serotonergic systems are a major target for drugs used to treat neuropsychiatric disorders such as depression and schizophrenia in which disruption of frontal cortex function has been implicated. However, it is not known precisely how serotonin (5-HT) modulates the medial prefrontal cortex (mPFC) to affect cognitive function and behaviour. OBJECTIVE: To investigate the roles of 5-HT(1A) and 5-HT(2A) receptors in mPFC on performance of the five-choice serial reaction time task (5CSRT), which assesses visuospatial attention, impulsivity and motivational processes. METHODS: Following training on the 5CSRT, rats were implanted with bilateral guide cannulae aimed at the mPFC. Rats received intra-mPFC infusions of either 8-OH-DPAT (10, 30 and 100 ng) or M100907 (30, 100 and 300 ng) according to a Latin square design. RESULTS: Both 8-OH-DPAT and M100907 selectively enhanced accuracy of target detection. When the stimulus duration was shortened, infusions of 8-OH-DPAT continued to improve accuracy, whereas M100907 decreased premature responding and omissions, thus partly dissociating the effects of these two compounds. Similar effects were obtained following systemic administration of M100907 and 8-OH-DPAT. The effects of 8-OH-DPAT were blocked by the 5-HT(1A) antagonist WAY 100635, at a dose that itself had no significant effects on behaviour. CONCLUSIONS: These results indicate that modulation of 5-HT function within the mPFC via distinct receptors can enhance performance on the 5CSRT. These findings suggest a mechanism by which serotonergic agents improve cognitive function, which may be relevant to their therapeutic benefit in the treatment of neuropsychiatric disorders.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed2002

Nucleus accumbens dopamine and discriminated approach learning: interactive effects of 6-hydroxydopamine lesions and systemic apomorphine administration.

RATIONALE: Although dopaminergic mechanisms have been implicated in incentive motivational processes, their role in appetitive conditioning remains poorly understood. OBJECTIVES: To investigate the effects of dopamine (DA) depleting lesions of the nucleus accumbens and the direct acting dopamine receptor agonist apomorphine on the learning of discriminated appetitive approach behavior in a Pavlovian autoshaping paradigm. METHODS: Rats received bilateral infusions of either phosphate-buffered saline (shams) or 6-hydroxydopamine (lesions) directly into the nucleus accumbens. Ten days later, rats were trained on an autoshaping task whereby a previously neutral light stimulus was paired with food reward. Presentation of another stimulus (CS-) was never followed by reward. Over 100 pairings subjects developed a conditioned response of approaching the reward-predictive stimulus (CS+). Prior to each autoshaping session subjects were administered either saline (1 ml/kg SC) or apomorphine (30 microg/kg; 100 microg/kg), in a between-subjects design. RESULTS: Lesioned subjects showed a delay in the acquisition of discriminated approach and were insensitive to a subsequent change in the contingency of the task whereby approaches to the CS+ now prevented food delivery. Low dose apomorphine profoundly impaired learning in both sham and lesioned subjects. Despite increasing the overall number of CS+ and CS- approaches, the higher dose of apomorphine allowed discriminated approach in sham-operated animals only. CONCLUSIONS: These data are compatible with the hypothesis that nucleus accumbens dopamine serves to energize rather than guide conditioned approach to appetitive cues. They also support the notion that DA inputs in this region confer flexibility of approach to cues predictive of reward.

Animals↗

PubMed2002

The frontal cortex of the rat and visual attentional performance: dissociable functions of distinct medial prefrontal subregions.

A previous study using a rodent five-choice test of attention found poor choice accuracy and increased perseverative responding following medial prefrontal cortex (mPFC) lesions. As this rat cortical area includes at least two anatomically distinguishable subregions, the present study investigated their specific contributions to performance of this task. Rats were trained on the five-choice task prior to receiving excitotoxic lesions or sham surgery. In the first experiment, lesions of the dorsal mPFC (Zilles's Cg1) resulted in poor accuracy, but no changes in perseverative responding. Introducing variable delays for stimulus presentation abolished these accuracy deficits, suggesting that Cg1-lesioned rats were impaired at using temporal cues to guide performance. In the second experiment, lesions of the ventral mPFC increased perseverative responding, but had only short-lasting effects on accuracy. Rats with complete mPFC lesions had both choice accuracy impairments and increased perseverative responding. Additional evidence of the functional dissociation of dorsal and ventral mPFC came from the analysis of the spatial and temporal distribution of the correct and incorrect responses. Only rats with ventral mPFC lesions showed delay-dependent deficits and bias towards a location that had recently been associated with reward. Taken together, these results suggest dissociable 'executive' functions of mPFC subregions. Circuits centred on Cg1 are critical for the temporal organization of behaviour, while networks involving the ventral mPFC are important for maintaining behavioural flexibility.

Animals↗

PubMedDate not supplied

Cholinergic modulation of visual attention and working memory: dissociable effects of basal forebrain 192-IgG-saporin lesions and intraprefrontal infusions of scopolamine.

Two experiments examined the effects of reductions in cortical cholinergic function on performance of a novel task that allowed for the simultaneous assessment of attention to a visual stimulus and memory for that stimulus over a variable delay within the same test session. In the first experiment, infusions of the muscarinic receptor antagonist scopolamine into the medial prefrontal cortex (mPFC) produced many omissions but did not impair rats' ability to correctly detect a brief visual stimulus. However, these animals were highly impaired in remembering the location of that stimulus following a delay period, although in a delay-independent manner. In the second experiment, another group of animals with selective 192 IgG-saporin lesions of the nucleus basalis magnocellularis (nBM) were not impaired under conditions of low-attentional demand. However, when the stimulus duration was reduced, a significant memory impairment was observed, but similar to the results of the first experiment, the nBM-lesioned animals were not impaired in attentional accuracy, although aspects of attention were compromised (e.g., omissions). These findings demonstrate that (1) cortical cholinergic depletion produces dissociable deficits in attention and memory, depending on the task demands, (2) delay-independent mnemonic deficits produced by scopolamine are probably due to impairments other than simple inattention, and (3) working memory deficits are not simply dependent on attentional difficulties per se. Together, these findings implicate the nBM cortical cholinergic system in both attentional and mnemonic processing.

Acetylcholine↗