Theta rhythms temporally coordinate sequences of hippocampal place cell ensembles during active behaviors, while sharp wave-ripples coordinate place cell sequences during rest. We investigated ...whether such coordination of hippocampal place cell sequences is disrupted during error trials in a delayed match-to-place task. As a reward location was learned across trials, place cell sequences developed that represented temporally compressed paths to the reward location during the approach to the reward location. Less compressed paths were represented on error trials as an incorrect stop location was approached. During rest periods of correct but not error trials, place cell sequences developed a bias to replay representations of paths ending at the correct reward location. These results support the hypothesis that coordination of place cell sequences by theta rhythms and sharp wave-ripples develops as a reward location is learned and may be important for the successful performance of a spatial memory task.
Continuous-attractor network models of grid formation posit that recurrent connectivity between grid cells controls their patterns of co-activation. Grid cells from a common module exhibit stable ...offsets in their periodic spatial tuning curves across environments, and this may reflect recurrent connectivity or correlated sensory inputs. Here we explore whether cell-cell relationships predicted by attractor models persist during sleep states in which spatially informative sensory inputs are absent. We recorded ensembles of grid cells in superficial layers of medial entorhinal cortex during active exploratory behaviors and overnight sleep. Per grid cell pair and collectively, and across waking, rapid eye movement sleep and non-rapid eye movement sleep, we found preserved patterns of spike-time correlations that reflected the spatial tuning offsets between these grid cells during active exploration. The preservation of cell-cell relationships across waking and sleep states was not explained by theta oscillations or activity in hippocampal subregion CA1. These results indicate that recurrent connectivity within the grid cell network drives grid cell activity across behavioral states.
Intrinsically stretchable bioelectronic devices based on soft and conducting organic materials have been regarded as the ideal interface for seamless and biocompatible integration with the human ...body. A remaining challenge is to combine high mechanical robustness with good electrical conduction, especially when patterned at small feature sizes. We develop a molecular engineering strategy based on a topological supramolecular network, which allows for the decoupling of competing effects from multiple molecular building blocks to meet complex requirements. We obtained simultaneously high conductivity and crack-onset strain in a physiological environment, with direct photopatternability down to the cellular scale. We further collected stable electromyography signals on soft and malleable octopus and performed localized neuromodulation down to single-nucleus precision for controlling organ-specific activities through the delicate brainstem.
Complex spatial working memory tasks have been shown to require both hippocampal sharp-wave ripple (SWR) activity and dentate gyrus (DG) neuronal activity. We therefore asked whether DG inputs to CA3 ...contribute to spatial working memory by promoting SWR generation. Recordings from DG and CA3 while rats performed a dentate-dependent working memory task on an eight-arm radial maze revealed that the activity of dentate neurons and the incidence rate of SWRs both increased during reward consumption. We then found reduced reward-related CA3 SWR generation without direct input from dentate granule neurons. Furthermore, CA3 cells with place fields in not-yet-visited arms preferentially fired during SWRs at reward locations, and these prospective CA3 firing patterns were more pronounced for correct trials and were dentate-dependent. These results indicate that coordination of CA3 neuronal activity patterns by DG is necessary for the generation of neuronal firing patterns that support goal-directed behavior and memory.
It remains unclear to what extent neurodevelopmental disorder (NDD) risk genes retain functions into adulthood and how they may influence disease phenotypes.
haploinsufficiency causes a severe NDD ...defined by autistic traits, cognitive impairment, and epilepsy. To determine if this gene retains therapeutically-relevant biological functions into adulthood, we performed a gene restoration technique in a mouse model for
haploinsufficiency. Adult restoration of SynGAP protein improved behavioral and electrophysiological measures of memory and seizure. This included the elimination of interictal events that worsened during sleep. These events may be a biomarker for generalized cortical dysfunction in
disorders because they also worsened during sleep in the human patient population. We conclude that SynGAP protein retains biological functions throughout adulthood and that non-developmental functions may contribute to disease phenotypes. Thus, treatments that target debilitating aspects of severe NDDs, such as medically-refractory seizures and cognitive impairment, may be effective in adult patients.
Interneurons expressing cholecystokinin (CCK) and parvalbumin (PV) constitute two key GABAergic controllers of hippocampal pyramidal cell output. Although the temporally precise and millisecond-scale ...inhibitory regulation of neuronal ensembles delivered by PV interneurons is well established, the in vivo recruitment patterns of CCK-expressing basket cell (BC) populations has remained unknown. We show in the CA1 of the mouse hippocampus that the activity of CCK BCs inversely scales with both PV and pyramidal cell activity at the behaviorally relevant timescales of seconds. Intervention experiments indicated that the inverse coupling of CCK and PV GABAergic systems arises through a mechanism involving powerful inhibitory control of CCK BCs by PV cells. The tightly coupled complementarity of two key microcircuit regulatory modules demonstrates a novel form of brain-state-specific segregation of inhibition during spontaneous behavior.
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•CA1 CCK basket cells are selectively labeled in the Sncg-Flp mouse line•CCK basket and PV cells display complementary activity during spontaneous behaviors•PV cells inhibit CCK basket cells in vivo•CCK basket cell activity inversely scales with the pyramidal cell ensemble activity
Dudok et al. show a complementary perisomatic inhibitory system consisting of CCK- and PV-expressing interneurons that are active at distinct times in an alternating fashion during spontaneous behaviors. Due to PV to CCK inhibition, CCK basket cells are the most active when PV and pyramidal cells are relatively silent.
Locomotor speed is a basic input used to calculate one’s position, but where this signal comes from is unclear. We identified neurons in the supramammillary nucleus (SuM) of the rodent hypothalamus ...that were highly correlated with future locomotor speed and reliably drove locomotion when activated. Robust locomotion control was specifically identified in
(substance P)–expressing (SuM
) neurons, the activation of which selectively controlled the activity of speed-modulated hippocampal neurons. By contrast,
-deficient (SuM
) cells weakly regulated locomotion but potently controlled the spike timing of hippocampal neurons and were sufficient to entrain local network oscillations. These findings emphasize that the SuM not only regulates basic locomotor activity but also selectively shapes hippocampal neural activity in a manner that may support spatial navigation.
At rest, hippocampal "place cells," neurons with receptive fields corresponding to specific spatial locations, reactivate in a manner that reflects recently traveled trajectories. These "replay" ...events have been proposed as a mechanism underlying memory consolidation, or the transfer of a memory representation from the hippocampus to neocortical regions associated with the original sensory experience. Accordingly, it has been hypothesized that hippocampal replay of a particular experience should be accompanied by simultaneous reactivation of corresponding representations in the neocortex and in the entorhinal cortex, the primary interface between the hippocampus and the neocortex. Recent studies have reported that coordinated replay may occur between hippocampal place cells and medial entorhinal cortex grid cells, cells with multiple spatial receptive fields. Assessing replay in grid cells is problematic, however, as the cells exhibit regularly spaced spatial receptive fields in all environments and, therefore, coordinated replay between place cells and grid cells may be detected by chance. In the present report, we adapted analytical approaches utilized in recent studies of grid cell and place cell replay to determine the extent to which coordinated replay is spuriously detected between grid cells and place cells recorded from separate rats. For a subset of the employed analytical methods, coordinated replay was detected spuriously in a significant proportion of cases in which place cell replay events were randomly matched with grid cell firing epochs of equal duration. More rigorous replay evaluation procedures and minimum spike count requirements greatly reduced the amount of spurious findings. These results provide insights into aspects of place cell and grid cell activity during rest that contribute to false detection of coordinated replay. The results further emphasize the need for careful controls and rigorous methods when testing the hypothesis that place cells and grid cells exhibit coordinated replay.
A popular model of memory consolidation posits that recent memories stored in the hippocampus are reactivated during sleep and thereby transferred to neocortex for long-term storage. This process is ...thought to occur during sharp wave-ripples (SWRs) in nonrapid eye movement sleep (NREM). However, whether the hippocampus consolidates all recent memories in the same manner remains unclear. An efficient memory system may extract novel information from recent experiences for preferential consolidation. In the hippocampus, memories are thought to be stored initially in CA3. Therefore, CA3 place cells that encode novel experiences may be preferentially reactivated during SWRs in subsequent sleep. To test this hypothesis, we recorded CA3 place cells in rats during exposure to a familiar and a novel environment and during subsequent overnight sleep. We found that CA3 place cells that preferentially coded a novel environment showed larger firing rate increases during SWRs in NREM than place cells that preferentially coded a familiar environment. Moreover, CA3 place cell ensembles replayed trajectories from a novel environment during NREM with higher fidelity than trajectories from a familiar environment. Together, these results suggest that CA3 representations of novel experiences are preferentially processed during subsequent sleep.
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