Biomedical subjects

Nancy S Hong

Publications and source records attributed to Nancy S Hong.

8 recordsLinked to original sources

PubMed2006

A double dissociation of dorsal and ventral hippocampal function on a learning and memory task mediated by the dorso-lateral striatum.

The objectives of this research were to further delineate the neural circuits subserving proposed memory-based behavioural subsystems in the hippocampal formation. These studies were guided by anatomical evidence showing a topographical organization of the hippocampal formation. Briefly, perpendicular to the medial/lateral entorhinal cortex division there is a second system of parallel circuits that separates the dorsal and ventral hippocampus. Recent work from this laboratory has provided evidence that the hippocampus incidentally encodes a context-specific inhibitory association during acquisition of a visual discrimination task. One question that emerges from this dataset is whether the dorsal or ventral hippocampus makes a unique contribution to this newly described function. Rats with neurotoxic lesions of the dorsal or ventral hippocampus were assessed on the acquisition of the visual discrimination task. Following asymptotic performance they were given reversal training in either the same or a different context from the original training. The results showed that the context-specific inhibition effect is mediated by a circuit that includes the ventral but not the dorsal hippocampus. Results from a control procedure showed that rats with either dorso-lateral striatum damage or dorsal hippocampal lesions were impaired on a tactile/spatial discrimination. Taken together, the results represent a double dissociation of learning and memory function between the ventral and dorsal hippocampus. The formation of an incidental inhibitory association was dependent on ventral but not dorsal hippocampal circuitry, and the opposite dependence was found for the spatial component of a tactile/spatial discrimination.

Animals↗

PubMed2005

Post-training intra-amygdala amphetamine injections given during acquisition of a stimulus-response (S-R) habit task enhance the expression of stimulus-reward learning: further evidence for incidental amygdala learning.

The effect of post-training intra-amygdala amphetamine injections was examined on the acquisition and expression of a visual discrimination task. Rats were trained to enter four lit arms for food (stimulus-response) and avoid unlit arms on an eight-arm radial maze visual discrimination task. Post-training intra-amygdala amphetamine injections (10 microg) were given for 4 consecutive days during the mid-point of training (days 20-23). The number of lit arm entries was used as a measure of stimulus-response habit learning 24 h after each injection. Twenty-four hours after the last injection, a transfer test was run to assess the effect of the same post-training manipulation. This transfer test assessed the amount of time spent in the lit arms and was used as a measure of stimulus-reward learning. Compared to saline-injected rats, rats that received post-training amphetamine spent more time in lit as opposed to dark arms during the transfer test. This occurred in the absence of an increase in the number of correct arm entries during visual discrimination training. This suggests that post-training amphetamine strengthened a stimulus-reward association that did not immediately affect behavioral output. This association may reflect a mnemonic representation stored in an ensemble of amygdala neurons.

Amphetamine↗

PubMed2005

Defective place cell activity in nociceptin receptor knockout mice with elevated NMDA receptor-dependent long-term potentiation.

There is growing evidence that NMDA receptor-dependent long-term potentiation (LTP) in the hippocampus mediates the synaptic plasticity that underlies spatial learning and memory. LTP deficiencies correlate well with spatial memory deficits and LTP enhancements may improve spatial memory. In addition, LTP deficiencies are associated with abnormal place cells as expected from the spatial mapping hypothesis of hippocampal function. In contrast, nothing is known on how enhanced NMDA receptor-dependent LTP affects place cells. To address this question we recorded place cells from mice lacking the nociceptin receptor (NOP1/ORL1/OP4) that have enhanced hippocampal LTP. We found that the enhanced LTP was mediated by NMDA receptors, did not require L-type calcium channels, and occurred only when high frequency tetanizing stimulus trains were used. Place cells in nociceptin receptor knockout mice were abnormal in several ways: they were less stable, had noisier positional firing patterns, larger firing fields and higher discharge rates inside and outside the firing fields. Our results suggest that excessive LTP can cause subnormal hippocampal place cell function. The effects of LTP enhancement on place cell function may therefore also depend on molecular details of synaptic plasticity, including the relationship between stimulus frequency and synaptic strength, and not merely on the magnitude of synaptic strength increases. The data have important clinical implications on development of strategies to improve cognitive function.

Action Potentials↗

PubMed2005

NMDA-receptor blockade by CPP impairs post-training consolidation of a rapidly acquired spatial representation in rat hippocampus.

Recent evidence suggests that N-methyl-D-aspartate (NMDA)-receptor mediated plasticity in hippocampus has a more subtle role in memory-based behaviours than originally thought. One idea is that NMDA-based plasticity is essential for the consolidation of post-training memory but not for the initial encoding or for short-term memory. To further test this idea we used a three-phase variant of the hidden goal water maze task. In the first phase, rats were pre-trained to an initial location. Next, intense, massed training was done in a 2-h interval to teach the rats to go to a new location after either an injection of the NMDA receptor antagonist (6)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) or of vehicle. Finally, under drug-free conditions 24 h after new location training, a competition test was done between the original and new locations. We find that N-methyl-D-aspartate (NMDA)-receptor blockade has little or no effect on new location training. In contrast, when tested 24 h later, the strength of the trace for the new location learned during NMDA-receptor blockade was much weaker compared with the trace for the new location learned after saline injection. Further experiments showed similar effects when NMDA-receptors were blocked immediately after the new location training, suggesting that this is a memory consolidation effect. Our results therefore reinforce the notion that hippocampal NMDA-receptors participate in post-training memory consolidation but are not essential for the processes necessary to learn or retain navigational information in the short term.

Animals↗

PubMed2004

Incidental information acquired by the amygdala during acquisition of a stimulus-response habit task.

In the present paper we tested the hypothesis that the amygdala incidentally acquires information during the acquisition of a task sensitive to damage to the dorso-lateral striatum. Two groups of rats were trained on a stimulus-response (S-R) habit task on the eight-arm radial maze. Prior to initial acquisition, one group received NMDA lesions of the amygdala and the other received sham surgeries. After reaching a strict learning criterion, both groups underwent reversal training in either the same or different context from original training. Consistent with our previous work, the sham group showed enhanced reversal learning in a context different from original training. The rats with amygdala damage showed a deficit in reversal learning in both contexts, although the deficit was more apparent in the different context. Both groups of rats that underwent reversal training in the context different from original training showed a normal competition effect for this task (chance performance) when they were returned to the initial training context. This data supports the idea that the second S-R association, acquired during reversal training, and the context-specific inhibitory association, acquired during original training, were unaffected by the amygdala damage. Taken together, this pattern of data suggests that the amygdala incidentally acquired information during the acquisition of the S-R habit task. The nature of the association acquired in this learning paradigm, and the implications of this finding for theories dealing with the organization and functions of mammalian learning and memory are discussed.

Amygdala↗

PubMed2004

The challenges of understanding mammalian cognition and memory-based behaviours: an interactive learning and memory systems approach.

Various research problems are presented to illustrate the utility of using the interactive multiple learning and memory systems view to better understand normal and abnormal manifestations of mammalian behaviour. Evidence for incidental learning and memory processes is presented and various implications of this work are discussed. Empirical and theoretical work directed at understanding the cognitive and non-cognitive processes associated with place learning in the water task and context conditioning during aversive events is also presented.

Amnesia, Retrograde↗

PubMed2004

Multiple memory systems: the power of interactions.

Two relatively simple theories of brain function will be used to demonstrate the explanatory power of multiple memory systems in your brain interacting cooperatively or competitively to directly or indirectly influence cognition and behaviour. The view put forth in this mini-review is that interactions between memory systems produce normal and abnormal manifestations of behaviour, and by logical extension, an understanding of these complex interactions holds the key to understanding debilitating brain and psychiatric disorders.

Amygdala↗

PubMed2002

Attenuation of context-specific inhibition on reversal learning of a stimulus-response task in rats with neurotoxic hippocampal damage.

Rats with hippocampal or sham lesions were trained on a stimulus-response task developed for the 8-arm radial maze. After reaching a stringent learning criterion, different context manipulations were performed. In Experiment I, the different groups were transferred to an identical radial maze in a different room to determine the context specificity of the discrimination learning. Experiment I revealed that although rats with hippocampal lesions did not show a normal context detection effect, the expression of the discrimination was not context dependent for either the lesion or sham groups. In Experiment II, animals were trained to criterion on the discrimination task and then both groups were divided into sub-groups based on whether they would experience reversal training in the same or different context from original training. Experiment II indicated that animals with hippocampal lesions and shams reversed in a different context were significantly enhanced in reaching the learning criterion compared to either counterparts that were reversed in the same context. Reversal learning in rats with hippocampal lesions was faster than sham animals in the same context suggesting that the context-specific inhibition effect was hippocampal-based. After learning the reversal task, the groups of animals trained and reversed in different contexts were brought back into the original training context to test for competitive effects. Animals with hippocampal lesions that were reversed in the different context, did not show a competition between the most recently acquired discrimination and a context-specific association acquired during original training whereas sham animals in the same condition did. Taken together these results suggest that rats with hippocampal lesions do not acquire normal context-specific inhibition during discrimination learning.

Animals↗