The hippocampal CA2 subregion has a different anatomical connectivity pattern within the entorhino-hippocampal circuit than either the CA1 or CA3 subregion. Yet major differences in the neuronal ...activity patterns of CA2 compared with the other CA subregions have not been reported. We show that standard spatial and temporal firing patterns of individual hippocampal principal neurons in behaving rats, such as place fields, theta modulation, and phase precession, are also present in CA2, but that the CA2 subregion differs substantially from the other CA subregions in its population coding. CA2 ensembles do not show a persistent code for space or for differences in context. Rather, CA2 activity patterns become progressively dissimilar over time periods of hours to days. The weak coding for a particular context is consistent with recent behavioral evidence that CA2 circuits preferentially support social, emotional, and temporal rather than spatial aspects of memory.
Calcium imaging using two-photon scanning microscopy has become an essential tool in neuroscience. However, in its typical implementation, the tradeoffs between fields of view, acquisition speeds, ...and depth restrictions in scattering brain tissue pose severe limitations. Here, using an integrated systems-wide optimization approach combined with multiple technical innovations, we introduce a new design paradigm for optical microscopy based on maximizing biological information while maintaining the fidelity of obtained neuron signals. Our modular design utilizes hybrid multi-photon acquisition and allows volumetric recording of neuroactivity at single-cell resolution within up to 1 × 1 × 1.22 mm volumes at up to 17 Hz in awake behaving mice. We establish the capabilities and potential of the different configurations of our imaging system at depth and across brain regions by applying it to in vivo recording of up to 12,000 neurons in mouse auditory cortex, posterior parietal cortex, and hippocampus.
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•In vivo Ca2+ imaging of ∼12,000 neurons in mouse cortex at single-cell resolution•Simultaneous 2p and 3p Ca2+ imaging within 1,000 × 1,000 × 1,220 μm at up to 17 Hz•Volumetric 3p Ca2+ imaging of hippocampus through intact cortex•A new integrated, systems-wide optimized microscopy design paradigm
A new volumetric calcium imaging method called hybrid multiplexed sculpted light microscopy (HyMS) opens up the window to record neuronal activity of more than 10,000 neurons over the entire cortical depth and within the hippocampus of awake and behaving mice.
Neuronal code for extended time in the hippocampus Mankin, Emily A; Sparks, Fraser T; Slayyeh, Begum ...
Proceedings of the National Academy of Sciences,
11/2012, Letnik:
109, Številka:
47
Journal Article
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The time when an event occurs can become part of autobiographical memories. In brain structures that support such memories, a neural code should exist that represents when or how long ago events ...occurred. Here we describe a neuronal coding mechanism in hippocampus that can be used to represent the recency of an experience over intervals of hours to days. When the same event is repeated after such time periods, the activity patterns of hippocampal CA1 cell populations progressively differ with increasing temporal distances. Coding for space and context is nonetheless preserved. Compared with CA1, the firing patterns of hippocampal CA3 cell populations are highly reproducible, irrespective of the time interval, and thus provide a stable memory code over time. Therefore, the neuronal activity patterns in CA1 but not CA3 include a code that can be used to distinguish between time intervals on an extended scale, consistent with behavioral studies showing that the CA1 area is selectively required for temporal coding over such periods.
The hippocampus plays a critical role in memory consolidation, mediated by coordinated network activity during sharp-wave ripple (SWR) events. Despite the link between SWRs and hippocampal ...plasticity, little is known about how network state affects information processing in dendrites, the primary sites of synaptic input integration and plasticity. Here, we monitored somatic and basal dendritic activity in CA1 pyramidal cells in behaving mice using longitudinal two-photon calcium imaging integrated with simultaneous local field potential recordings. We found immobility was associated with an increase in dendritic activity concentrated during SWRs. Coincident dendritic and somatic activity during SWRs predicted increased coupling during subsequent exploration of a novel environment. In contrast, somatic-dendritic coupling and SWR recruitment varied with cells’ tuning distance to reward location during a goal-learning task. Our results connect SWRs with the stabilization of information processing within CA1 neurons and suggest that these mechanisms may be dynamically biased by behavioral demands.
•Basal dendrites of mouse CA1 pyramidal cells coactivate with the soma during SWRs•Activity during SWRs in novel environments predicts future soma-dendrite coupling•Dendritic tuning dissociates from somatic firing during spatial reward learning•Cells tuned far from reward show increased dendritic coactivity and SWR recruitment
Rolotti et al. combine calcium imaging and electrophysiology to study somatic-dendritic dynamics across behavior and network states in mouse hippocampus. Sharp-wave ripples modulate dendritic activity, inducing long-term changes in soma-dendrite coupling. Reinforcement alters ripple recruitment and dissociates dendritic-somatic spatial tuning. Ripples may facilitate dendritic reorganization to stabilize hippocampal computations.
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.
Spatial memories that can last a lifetime are thought to be encoded during 'online' periods of exploration and subsequently consolidated into stable cognitive maps through their 'offline' ...reactivation. However, the mechanisms and computational principles by which offline reactivation stabilize long-lasting spatial representations remain poorly understood. Here, we employed simultaneous fast calcium imaging and electrophysiology to track hippocampal place cells over 2 weeks of online spatial reward learning behavior and offline resting. We describe that recruitment to persistent network-level offline reactivation of spatial experiences in mice predicts the future representational stability of place cells days in advance of their online reinstatement. Moreover, while representations of reward-adjacent locations are generally more stable across days, offline-reactivation-related stability is, conversely, most prominent for reward-distal locations. Thus, while occurring on the tens of milliseconds timescale, offline reactivation is uniquely associated with the stability of multiday representations that counterbalance the overall reward-adjacency bias, thereby predicting the stabilization of cognitive maps that comprehensively reflect entire underlying spatial contexts. These findings suggest that post-learning offline-related memory consolidation plays a complimentary and computationally distinct role in learning compared to online encoding.
Hippocampal place cells underlie spatial navigation and memory. Remarkably, CA1 pyramidal neurons can form new place fields within a single trial by undergoing rapid plasticity. However, local ...feedback circuits likely restrict the rapid recruitment of individual neurons into ensemble representations. This interaction between circuit dynamics and rapid feature coding remains unexplored. Here, we developed “all-optical” approaches combining novel optogenetic induction of rapidly forming place fields with 2-photon activity imaging during spatial navigation in mice. We find that induction efficacy depends strongly on the density of co-activated neurons. Place fields can be reliably induced in single cells, but induction fails during co-activation of larger subpopulations due to local circuit constraints imposed by recurrent inhibition. Temporary relief of local inhibition permits the simultaneous induction of place fields in larger ensembles. We demonstrate the behavioral implications of these dynamics, showing that our ensemble place field induction protocol can enhance subsequent spatial association learning.
•Rapidly forming place fields can be optogenetically induced in mouse CA1 neurons•Feedback inhibition limits rapid place field induction to fewer principal neurons•Suppressing local inhibition allows induction of place fields in larger ensembles•Ensemble place field induction can enhance subsequent spatial association learning
Rolotti, Ahmed, Szoboszlay et al. develop “all-optical” strategies to induce rapidly forming place fields in mouse CA1 and find that local feedback inhibition restricts recruitment of neurons into ensemble representations. Temporary relief of local inhibition permits the simultaneous induction of place fields in larger ensembles to enhance subsequent association learning.
Behavior is used to assess memory and cognitive deficits in animals like Fmr1-null mice that model Fragile X Syndrome, but behavior is a proxy for unknown neural events that define cognitive ...variables like recollection. We identified an electrophysiological signature of recollection in mouse dorsal Cornu Ammonis 1 (CA1) hippocampus. During a shocked-place avoidance task, slow gamma (SG) (30-50 Hz) dominates mid-frequency gamma (MG) (70-90 Hz) oscillations 2-3 s before successful avoidance, but not failures. Wild-type (WT) but not Fmr1-null mice rapidly adapt to relocating the shock; concurrently, SG/MG maxima (SGdom) decrease in WT but not in cognitively inflexible Fmr1-null mice. During SGdom, putative pyramidal cell ensembles represent distant locations; during place avoidance, these are avoided places. During shock relocation, WT ensembles represent distant locations near the currently correct shock zone, but Fmr1-null ensembles represent the formerly correct zone. These findings indicate that recollection occurs when CA1 SG dominates MG and that accurate recollection of inappropriate memories explains Fmr1-null cognitive inflexibility.
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.
Neurological and psychiatric disorders are associated with pathological neural dynamics. The fundamental connectivity patterns of cell-cell communication networks that enable pathological dynamics to ...emerge remain unknown. Here, we studied epileptic circuits using a newly developed computational pipeline that leveraged single-cell calcium imaging of larval zebrafish and chronically epileptic mice, biologically constrained effective connectivity modeling, and higher-order motif-focused network analysis. We uncovered a novel functional cell type that preferentially emerged in the preseizure state, the superhub, that was unusually richly connected to the rest of the network through feedforward motifs, critically enhancing downstream excitation. Perturbation simulations indicated that disconnecting superhubs was significantly more effective in stabilizing epileptic circuits than disconnecting hub cells that were defined traditionally by connection count. In the dentate gyrus of chronically epileptic mice, superhubs were predominately modeled adult-born granule cells. Collectively, these results predict a new maximally selective and minimally invasive cellular target for seizure control.
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•Motif patterns of epileptic networks were inferred from single-cell calcium data•Superhubs rich in excitatory feedforward motifs emerged in the preseizure state•Disconnecting superhubs effectively stabilized epileptic circuits in simulations•Superhubs are predicted to be adult-born granule cells in the mouse dentate gyrus
Hadjiabadi et al. reveal a novel functional cell type, the superhub, that preferentially emerges in the preseizure brain to powerfully propagate excitation. Disconnecting superhubs in simulations stabilizes epileptic circuits more effectively than disconnecting traditional hubs, predicting a new single-cell target for seizure control.
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