A specific memory is thought to be encoded by a sparse population of neurons1,2. These neurons can be tagged during learning for subsequent identification3 and manipulation4,5,6. Moreover, their ablation or inactivation results in reduced memory expression, suggesting their necessity in mnemonic processes. However, a critical question of sufficiency remains: can one elicit the behavioral output of a specific memory by directly activating a population of neurons that was active during learning? Here we show that optogenetic reactivation of hippocampal neurons activated during fear conditioning is sufficient to induce freezing behavior. We labeled a population of hippocampal dentate gyrus neurons activated during fear learning with channelrhodopsin-2 (ChR2)7,8 and later optically reactivated these neurons in a different context. The mice showed increased freezing only upon light stimulation, indicating light-induced fear memory recall. This freezing was not detected in non-fear conditioned mice expressing ChR2 in a similar proportion of cells, nor in fear conditioned mice with cells labeled by EYFP instead of ChR2. Finally, activation of cells labeled in a context not associated with fear did not evoke freezing in mice that were previously fear conditioned in a different context, suggesting that light-induced fear memory recall is context-specific. Together, our findings indicate that activating a sparse but specific ensemble of hippocampal neurons that contribute to a memory engram is sufficient for the recall of that memory. Moreover, our experimental approach offers a general method of mapping cellular populations bearing memory engrams.

As one of the two main sources of brain dopamine, the ventral tegmental area (VTA) is important for several complex functions, including motivation, reward prediction, and contextual learning. Although many studies have identified the potential neural substrate of VTA dopaminergic activity in reward prediction functions during Pavlovian and operant conditioning tasks, less is understood about the role of VTA neuronal activity in motivated behaviors and more naturalistic forms of context-dependent learning. Therefore, VTA neural activity was recorded as rats performed a spatial memory task under varying context conditions. In addition to reward-and reward predicting cuerelated firing commonly observed during conditioning tasks, the activity of a large proportion of VTA neurons was also related to the velocity and/or acceleration of the animal's movement. Importantly, movement-related activity was strongest when rats displayed more motivation to obtain reward. Furthermore, many cells displayed a dual code of movement-and reward-related activity. These two modes of firing, however, were differentially regulated by context information, suggesting that movement-and reward-related firing are two independently regulated modes of VTA neuronal activity and may serve separate functions.

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Cerebral artery vasospasm is a major cause of death and disability in patients experiencing subarachnoid hemorrhage (SAH). Currently, little is known regarding the impact of SAH on small diameter (100–200 μm) cerebral arteries, which play an important role in the autoregulation of cerebral blood flow. With the use of a rabbit SAH model and in vitro video microscopy, cerebral artery diameter was measured in response to elevations in intravascular pressure. Cerebral arteries from SAH animals constricted more (∼twofold) to pressure within the physiological range of 60–100 mmHg compared with control or sham-operated animals. Pressure-induced constriction (myogenic tone) was also enhanced in arteries from control animals organ cultured in the presence of oxyhemoglobin, an effect independent of the vascular endothelium or nitric oxide synthesis. Finally, arteries from both control and SAH animals dilated as intravascular pressure was elevated above 140 mmHg. This study provides evidence for a role of oxyhemoglobin in impaired autoregulation (i.e., enhanced myogenic tone) in small diameter cerebral arteries during SAH. Furthermore, therapeutic strategies that improve clinical outcome in SAH patients (e.g., supraphysiological intravascular pressure) are effective in dilating small diameter cerebral arteries isolated from SAH animals.

ABSTRACT:There is substantial evidence that hippocampus plays an important role in the processing of contextual information. Its specific role, however, remains unclear. One possibility is that single hippocampal neurons represent context information so that local circuits can construct representations of the current context, and the context that is expected based on past experience. Population codes derived from input by multiple local circuits may then engage match-mismatch algorithms that compare current and expected context information to determine the extent to which an expected context has changed. The results of such match-mismatch comparisons can be used to discriminate contexts. When context changes are detected, efferent messages may be passed on to connected neocortical areas so that informed "decisions" regarding future behavioral and cognitive strategies can be made. Here, a brief review describes evidence that a primary consequence of hippocampal processing is the discrimination of meaningful contexts. Then, the functional significance of neocortical circuits that likely receive hippocampal output messages are described in terms of their contribution to the control of ongoing behavioral and cognitive strategy, especially during active navigation. It is clear from this systems view that studies of spatial navigation continue to provide researchers with an excellent model of hippocampal-neocortical interactions during learning. V V C 2007 Wiley-Liss, Inc.