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Rodents exhibit neophobia for novel tastes, demonstrated by an initial reluctance to drink novel-tasting, potentially-aversive solutions. Taste neophobia attenuates across days if the solution is not aversive, demonstrated by increased consumption as the solution becomes familiar. This attenuation of taste neophobia is context dependent, which has been demonstrated by maintained reluctance to drink the novel tasting solution if the subject has to drink it after being brought to a novel environment. This spatial context-dependent attenuation of taste neophobia has been described and likely depends on the integrity of the dorsal hippocampus because this brain area is crucial for representing space and spatial context associations, but is unnecessary for processing taste memories per se. Whether changing the non-spatial auditory context causes a similar effect on attenuation of taste neophobia and the potential role of the dorsal hippocampus in processing this decidedly non-spatial information has not been determined. Here we demonstrate that changing the non-spatial auditory context affects the attenuation of taste neophobia in mice, and investigate the consequence of hippocampal lesion. The results demonstrate that the non-spatial auditory context-dependent attenuation of taste neophobia in mice is lost following NMDA excitotoxic lesions of the CA1 region of the dorsal hippocampus. These findings demonstrate that the dorsal hippocampus is crucial for the modulation non-associative taste learning by auditory context, neither of which provide information about space., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

PKMζ is an autonomously active PKC isoform that is thought to maintain both LTP and long-term memory. Whereas persistent increases in PKMζ protein sustain the kinase's action in LTP, the molecular mechanism for the persistent action of PKMζ during long-term memory has not been characterized. PKMζ inhibitors disrupt spatial memory when introduced into the dorsal hippocampus from 1day to 1month after training. Therefore, if the mechanisms of PKMζ's persistent action in LTP maintenance and long-term memory were similar, persistent increases in PKMζ would last for the duration of the memory, far longer than most other learning-induced gene products. Here we find that spatial conditioning by aversive active place avoidance or appetitive radial arm maze induces PKMζ increases in dorsal hippocampus that persist from 1day to 1month, coinciding with the strength and duration of memory retention. Suppressing the increase by intrahippocampal injections of PKMζ-antisense oligodeoxynucleotides prevents the formation of long-term memory. Thus, similar to LTP maintenance, the persistent increase in the amount of autonomously active PKMζ sustains the kinase's action during long-term and remote spatial memory maintenance., (Copyright © 2016. Published by Elsevier Inc.)

A widely accepted notion for a process underlying memory formation is that learning changes the efficacy of synapses by the mechanism of synaptic plasticity. While there is compelling evidence of changes in synaptic efficacy observed after learning, demonstration of persistent synaptic changes accompanying memory has been elusive. We report that acquisition of a hippocampus and long-term potentiation dependent place memory persistently changes the function of CA1 synapses. Using extracellular recordings we measured CA3-CA1 and EC-CA1 synaptic responses and found robust changes in the CA3-CA1 pathway after memory training. Crucially, these changes in synaptic function lasted at least a month and coincided with the persistence of long-term place memories; the changes were only observed in animals that expressed robust memory, and not in animals with poor memory recall. Interestingly, our findings were observed at the level of populations of synapses; suggesting that memory formation recruits widespread synaptic circuits and persistently reorganizes their function to store information., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Recently, protein kinase M ζ (PKMζ) has emerged as an important player for maintaining memory. It has been reported that PKMζ regulates the trafficking of GluA2 in postsynaptic membranes to maintain memory. However, there has been no study on PKMζ outside the synaptic region regarding memory maintenance. Here, we found that PKMζ is transported to the nucleus in a neural activity-dependent manner. Moreover, we found that PKMζ phosphorylates CREB-binding protein (CBP) at serine residues and that PKMζ inhibition reduces the acetylation of histone H2B and H3. Finally, we showed that the amnesic effect of PKMζ inhibition can be rescued by enhancing histone acetylation level. These results suggest the possibility that nuclear PKMζ has a crucial role in memory maintenance., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The processes that organize different thoughts and memories, allowing the separation of currently relevant and irrelevant information, are collectively known as cognitive control. The neuronal mechanisms of these processes can be investigated by place cell ensemble recordings during behaviors and environmental manipulations that present cognitive control challenges to selectively represent one of multiple possible alternative estimates of location. We review place cell studies that investigate responses to manipulations that dissociate the environment into two or more spatial frames of locations, often times to test notions of pattern separation. Manipulations, such as continuously rotating the recording chamber reveal that the ensemble discharge in hippocampus self-organizes into multiple, transiently-organized representations of space, each defined by the subset of coactive cells. Ensemble discharge in the hippocampus alternates between separate representations of frame-specific positions on timescales from 25 ms to several seconds. The dynamic, functional grouping of discharge into transiently co-active subsets of cells is predicted by the animal's changing behavioral needs. In addition to identifying neural correlates of cognitive control in hippocampus, these observations demonstrate that the separation of neuronal activity into distinctive representations depends on ongoing cognitive demands and that what can appear as noise, deviations from receptive field tuning, can substantially be the result of these internal knowledge-guided fluctuations. These findings inspire a new perspective that should be taken into account when investigating pattern separation--a perspective that emphasizes changes in hippocampal neural discharge that are happening on a short timescale and does not assume that patterns of neural discharge are steady and stationary across the several minutes of the recordings., (Copyright © 2016 Elsevier Inc. All rights reserved.)