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There is limited knowledge regarding how the brain controls the timing of meals. Similarly, there is a large gap in our understanding of how top-down cognitive processes, such as memory influence energy intake. We hypothesize that dorsal hippocampal (dHC) neurons, which are critical for episodic memory, form a memory of a meal and inhibit meal onset during the postprandial period. In support, we showed previously that reversible inactivation of these neurons during the period following a sucrose meal accelerates the onset of the next meal. If dHC neurons form a memory of a meal, then consumption should induce synaptic plasticity in dHC neurons. To test this, we determined (1) whether a sucrose meal increases the expression of the synaptic plasticity marker activity-regulated cytoskeleton-associated protein (Arc) in dHC CA1 neurons, (2) whether previous experience with sucrose influences sucrose-induced Arc expression, and (3) whether the orosensory stimulation produced by the noncaloric sweetener saccharin is sufficient to induce Arc expression. Male Sprague-Dawley rats were trained to consume a sweetened solution at a scheduled time daily. On the experimental day, they were given a solution for 7 min, euthanized, and then fluorescence in situ hybridization procedures were used to measure meal-induced Arc mRNA. Compared to caged control rats, Arc expression was significantly higher in rats that consumed sucrose or saccharin. Interestingly, rats given additional experience with sucrose had less Arc expression than rats with less sucrose experience, even though both groups consumed similar amounts on the experimental day. Thus, this study is the first to suggest that orosensory stimulation produced by consuming a sweetened solution and possibly the hedonic value of that sweet stimulation induces synaptic plasticity in dHC CA1 neurons in an experience-dependent manner. Collectively, these findings are consistent with our hypothesis that dHC neurons form a memory of a meal.

Active behavior, such as exploring a novel environment, induces the expression of the immediate-early gene Arc (activity-regulated cytoskeletal associated protein, or Arg 3.1) in many brain regions, including the hippocampus, neocortex, and striatum. Arc messenger ribonucleic acid and protein are localized in activated dendrites, and Arc protein is required for the maintenance of long-term potentiation and memory consolidation. Although previous evidence suggests that Arc is expressed in neurons, there is no direct demonstration that only neurons can express Arc. Furthermore, there is no characterization of the main neuronal types that express Arc. The data reported here show that behavior- or seizure-induced Arc expression in the hippocampus, primary somatosensory cortex, and dorsal striatum of rats colocalizes only with neuronal (NeuN-positive) and not with glial (GFAP-positive) cells. Furthermore, Arc was found exclusively in non-GABAergic alpha-CaMKII-positive hippocampal and neocortical neurons of rats that had explored a novel environment. Some GAD65/67-positive neurons in these regions were observed to express Arc, but only after a very strong stimulus (electroconvulsive seizure). In the dorsal striatum, spatial exploration induced Arc only in GABAergic and alpha-CaMKII-positive neurons. Combined, these results show that although a very strong stimulus (seizure) can induce Arc in a variety of neurons, behavior induces Arc in the CaMKII-positive principal neurons of the hippocampus, neocortex, and dorsal striatum. These results, coupled with recent in vitro findings of interactions between Arc and CaMKII, are consistent with the hypothesis that Arc and CaMKII act as plasticity partners to promote functional and/or structural synaptic modifications that accompany learning.

Lesions of the lateral/basolateral amygdala nuclei (BLC) disrupt freezing behaviour in response to explicit or contextual cues (conditioned stimuli--CS) paired previously with footshock (unconditioned stimulus). This deficit in expression of defensive behaviour in response to conditioned stimuli is often interpreted as inability of lesioned rats to learn CS-US associations. However, findings of several studies indicate that BLC-lesioned rats can rapidly learn CS-US associations. Such findings suggest that lesioned rats can learn CS-US associations but are impaired in the expression of freezing behaviour. In the present study we report that both temporary inactivation (lidocaine) and permanent excitotoxic (NMDA) lesions of the BLC impair the unconditioned freezing and avoidance behaviours of rats in response to a novel fear-eliciting stimulus, a ball of cat hair. These findings suggest that the BLC influences the expression of freezing and avoidance behaviours, and/or that it potentiates rats' experience of fear. Along with prior evidence of spared memory for aversive learning after BLC lesions, these findings suggest that disrupted freezing to conditioned cues in BLC-lesioned rats does not necessarily reflect inability to form CS-US associations.

A major hypothesis about lateral/basolateral amygdala complex (BLC) function in memory proposes that the BLC is the site where conditioned stimulus–unconditioned stimulus (CS–US) associations are formed and permanently stored during Pavlovian ‘fear conditioning.’ Thus, according to this hypothesis, the BLC is necessary for the acquisition and expression of both discrete-cue and contextual Pavlovian fear conditioning. This hypothesis clearly requires that animals with complete lesions of the BLC be completely unable to acquire Pavlovian fear conditioning. In this experiment, distribution of training and testing trials over three sessions revealed that rats with complete BLC lesions rapidly acquired a contextual CS–US association (as assessed with freezing behaviour), although their performance, as expected, did not equal that of sham operated controls. Irrespective of the nature of the freezing deficit relative to controls, the learning in the BLC-lesioned rats strongly indicates that Pavlovian fear conditioning CS–US associations can be rapidly acquired in the absence of the BLC, and that the BLC cannot therefore be necessary for their acquisition.