RESUMEN
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.
Asunto(s)
Microscopía/métodos , Imagen Molecular/métodos , Neuroimagen/métodos , Animales , Encéfalo/fisiología , Calcio/metabolismo , Femenino , Hipocampo/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Neuronas/fisiología , Análisis de la Célula Individual/métodosRESUMEN
The hippocampal formation plays a central role in the development of temporal lobe epilepsy (TLE), a disease characterized by recurrent, unprovoked epileptic discharges. TLE is a neurologic disorder characterized by acute long-lasting seizures (i.e., abnormal electrical activity in the brain) or seizures that occur in close proximity without recovery, typically after a brain injury or status epilepticus. After status epilepticus, epileptogenic hyperexcitability develops gradually over the following months to years, resulting in the emergence of chronic, recurrent seizures. Acting as a filter or gate, the hippocampal dentate gyrus (DG) normally prevents excessive excitation from propagating through the hippocampus, and is considered a critical region in the progression of epileptogenesis in pathological conditions. Importantly, lipid-derived endogenous cannabinoids (endocannabinoids), which are produced on demand as retrograde messengers, are central regulators of neuronal activity in the DG circuit. In this review, we summarize recent findings concerning the role of the DG in controlling hyperexcitability and propose how DG regulation by cannabinoids (CBs) could provide avenues for therapeutic interventions. We also highlight possible pathways and manipulations that could be relevant for the control of hyperexcitation. The use of CB compounds to treat epilepsies is controversial, as anecdotal evidence is not always validated by clinical trials. Recent publications shed light on the importance of the DG as a region regulating incoming hippocampal excitability during epileptogenesis. We review recent findings concerning the modulation of the hippocampal DG circuitry by CBs and discuss putative underlying pathways. A better understanding of the mechanisms by which CBs exert their action during seizures may be useful to improve therapies.
Asunto(s)
Cannabinoides , Epilepsia del Lóbulo Temporal , Epilepsia , Estado Epiléptico , Humanos , Animales , Hipocampo/patología , Convulsiones/patología , Epilepsia/etiología , Epilepsia/patología , Epilepsia del Lóbulo Temporal/patología , Neuronas/patología , Estado Epiléptico/patología , Giro Dentado/patología , Modelos Animales de EnfermedadRESUMEN
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.
Asunto(s)
Región CA1 Hipocampal/fisiología , Memoria/fisiología , Animales , Biomarcadores , Ondas Encefálicas/fisiología , Trastornos del Conocimiento/fisiopatología , Disfunción Cognitiva/fisiopatología , Modelos Animales de Enfermedad , Fenómenos Electrofisiológicos/fisiología , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/fisiología , Rayos gamma , Ritmo Gamma/fisiología , Hipocampo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Células Piramidales , Lóbulo TemporalRESUMEN
Training in the active place avoidance task changes hippocampus synaptic function, the dynamics of hippocampus local field potentials, place cell discharge, and active place avoidance memory is maintained by persistent PKMζ activity. The extent to which these changes reflect memory processes and/or stress responses is unknown. We designed a study to assess stress within the active place avoidance task by measuring serum corticosterone (CORT) at different stages of training. CORT levels did not differ between trained mice that learned to avoid the location of the mild foot shock, and untrained no-shock controls exposed to the same environment for the same amount of time. Yoked mice, that received unavoidable shocks in the same time sequence as the trained mice, had significantly higher CORT levels than mice in the trained and no-shock groups after the first trial. This increase in CORT disappeared by the fourth trial the following day, and levels of CORT for all groups matched that of home cage controls. The data demonstrate that place avoidance training is no more stressful than experiencing a familiar environment. We conclude that changes in neural function as a result of active place avoidance training are likely to reflect learning and memory processes rather than stress. © 2016 Wiley Periodicals, Inc.
Asunto(s)
Reacción de Prevención/fisiología , Corticosterona/sangre , Conducta Exploratoria/fisiología , Reconocimiento en Psicología/fisiología , Estrés Psicológico/sangre , Animales , Electrochoque , Masculino , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Pruebas Neuropsicológicas , Navegación Espacial/fisiologíaRESUMEN
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.
Asunto(s)
Hipocampo/citología , Hipocampo/fisiología , Neuronas/fisiología , Potenciales de Acción/fisiología , Animales , Región CA1 Hipocampal/citología , Región CA1 Hipocampal/fisiología , Región CA3 Hipocampal/citología , Región CA3 Hipocampal/fisiología , Masculino , Modelos Neurológicos , Ratas , Ratas Long-Evans , Factores de TiempoRESUMEN
The standard model of systems consolidation holds that the hippocampus (HPC) is involved only in the initial storage and retrieval of a memory. With time hippocampal-neocortical interactions slowly strengthen the neocortical memory, ultimately enabling retrieval of the memory without the HPC. Key support for this idea comes from experiments measuring memory recall in the socially-transmitted food preference (STFP) task in rats. HPC damage within a day or two of STFP learning can abolish recall, but similar damage five or more days after learning has no effect. We hypothesize that disruption of cellular consolidation outside the HPC could contribute to the amnesia with recent memories, perhaps playing a more important role than the loss of HPC. This view predicts that intraHPC infusion of Tetrodotoxin (TTX), which can block conduction of action potentials from the lesion sites, will block the retrograde amnesia in the STFP task. Here we confirm the previously reported retrograde amnesia with neurotoxic HPC damage within the first day after learning, but show that co-administration of TTX with the neurotoxin blocks the retrograde amnesia despite very extensive HPC damage. These results indicate that HPC damage disrupts cellular consolidation of the recent memory elsewhere; STFP memory may not ever depend on the HPC.
Asunto(s)
Comunicación Animal , Preferencias Alimentarias/fisiología , Hipocampo/fisiología , Recuerdo Mental/fisiología , Conducta Social , Animales , Hipocampo/efectos de los fármacos , Aprendizaje/efectos de los fármacos , Aprendizaje/fisiología , Masculino , Recuerdo Mental/efectos de los fármacos , Ratas , Bloqueadores de los Canales de Sodio/farmacología , Tetrodotoxina/farmacologíaRESUMEN
There are still basic uncertainties concerning the role of the hippocampus (HPC) in maintaining long-term context memories. All experiments examining the effects of extensive HPC damage on context memory for a single learning episode find that damage soon after learning results in robust retrograde amnesia. Some experiments find that if the learning-to-damage interval is extended, remote context memories are spared. In contrast, other experiments fail to find spared remote context memory. One possible explanation for inconsistency might be the potency of the context memory conditioning procedure, as the experiments showing spared remote memory used a greater number of context-shock pairings, likely creating a stronger context fear memory. We designed an experiment to directly test the question: does increasing the number of context-shock pairings result in sparing of remote context memory after HPC damage? Six independent groups of rats received either 3 or 12 context-shock pairings during a single conditioning session and then either received extensive HPC damage or Control surgery at 1-week, 2-months, or 4-months after conditioning. 10 days after surgery rats were tested for memory of the shock context. Consistent with all relevant studies, HPC damage at the shortest training-surgery interval produced robust retrograde amnesia for both 3- and 12-shock groups whereas the Control rats expressed significantly high levels of memory. At the longer training-surgery interval, HPC damage produced similarly robust retrograde amnesia in the rats in both the 3- and 12-shock groups. These results clearly demonstrate that increasing the number of context-shock pairings within a single learning session does not change the dependence of the memory on the HPC. Current evidence from our group on retrograde amnesia has now shown that partial damage, dorsal vs. ventral damage, discrete cue+context conditioning, time after training, and number of context-shock pairings do not affect HPC dependence of context fear memories. When taken together, the evidence strongly supports a permanent role of the HPC in context memory.
Asunto(s)
Amnesia Retrógrada/fisiopatología , Condicionamiento Clásico/fisiología , Hipocampo/fisiopatología , Memoria a Largo Plazo/efectos de los fármacos , Memoria a Largo Plazo/fisiología , Animales , Condicionamiento Clásico/efectos de los fármacos , Electrochoque , Reacción Cataléptica de Congelación/efectos de los fármacos , Reacción Cataléptica de Congelación/fisiología , Hipocampo/efectos de los fármacos , Masculino , N-Metilaspartato/toxicidad , Ratas , Ratas Long-EvansRESUMEN
An animal confronts numerous challenges when constructing an optimal navigational route. Spatial representations used for path optimization are likely constrained by critical environmental factors that dictate which neural systems control navigation. Multiple coding schemes depend upon their ecological relevance for a particular species, particularly when dealing with the third, or vertical, dimension of space.
Asunto(s)
Cognición/fisiología , Modelos Neurológicos , Percepción Espacial/fisiología , Conducta Espacial , Animales , HumanosRESUMEN
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.
Asunto(s)
Hipocampo , Consolidación de la Memoria , Animales , Región CA1 Hipocampal/fisiología , Hipocampo/fisiología , Ratones , Neuronas , Células Piramidales/fisiologíaRESUMEN
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.
Asunto(s)
Hipocampo , Células de Lugar , Animales , Región CA1 Hipocampal/fisiología , Retroalimentación , Hipocampo/fisiología , Ratones , Neuronas/fisiología , Células Piramidales/fisiologíaRESUMEN
Context memories normally depend on the hippocampus (HPC) but, in the absence of the HPC, other memory systems are capable of acquiring and supporting these memories. This suggests that the HPC can interfere with other systems during memory acquisition. Here we ask whether the HPC can also interfere with the retrieval of a context memory that was independently acquired by a non-HPC system. Specifically, we assess whether the HPC can impair the retrieval of a contextual fear-conditioning memory that was acquired while the HPC was temporarily inactive. Rats were infused with the γ-aminobutyric acid (GABA)(A) receptor agonist muscimol in the dorsal and ventral HPC either before acquisition, retrieval, or prior to both acquisition and retrieval, consistent with the effects of permanent HPC lesions on contextual fear conditioning, if the HPC was inactive at the time of acquisition and retention memory was intact. Thus, non-HPC systems acquired and supported this memory in absence of the HPC. However, if the HPC was inactive during acquisition but active thereafter, rats displayed severe deficits during the retention test. Moreover, when the same rats received a second retention test but with the HPC inactive at this time, the memory was recovered, suggesting that removal of a form of interference allowed the memory to be expressed. Combined, these findings imply that the HPC competes and/or interferes with retrieval of a long-term memory that was established in non-HPC systems.
Asunto(s)
Condicionamiento Clásico/fisiología , Miedo/fisiología , Hipocampo/fisiología , Memoria/fisiología , Amnesia , Animales , Condicionamiento Clásico/efectos de los fármacos , Femenino , Agonistas de Receptores de GABA-A/farmacología , Hipocampo/efectos de los fármacos , Hipocampo/patología , Masculino , Memoria/efectos de los fármacos , Muscimol/farmacología , Pruebas Neuropsicológicas , Ratas , Ratas Long-EvansRESUMEN
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.
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Mapeo Encefálico/métodos , Cognición/fisiología , Hipocampo/fisiología , Consolidación de la Memoria/fisiología , Células de Lugar/fisiología , Conducta Espacial/fisiología , Animales , Predicción , Hipocampo/citología , Ratones , Ratones Endogámicos C57BL , Ratones TransgénicosRESUMEN
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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Comunicación Celular/fisiología , Epilepsia/fisiopatología , Neuronas/fisiología , Convulsiones/fisiopatología , Animales , Giro Dentado/patología , Giro Dentado/fisiopatología , Red Nerviosa/fisiopatología , Pez CebraRESUMEN
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 Tac1 (substance P)expressing (SuMTac1+) neurons, the activation of which selectively controlled the activity of speed-modulated hippocampal neurons. By contrast, Tac1-deficient (SuMTac1−) 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.
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Hipocampo/fisiología , Hipotálamo Posterior/fisiología , Locomoción , Neuronas/fisiología , Potenciales de Acción , Animales , Hipocampo/citología , Hipotálamo Posterior/citología , Ratones , Ratones Endogámicos C57BL , Vías Nerviosas/fisiología , Ratas , Navegación Espacial , Sustancia P/genética , Ritmo TetaRESUMEN
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.
Asunto(s)
Región CA1 Hipocampal/fisiología , Interneuronas/fisiología , Células Piramidales/fisiología , Transmisión Sináptica/fisiología , Animales , Colecistoquinina/metabolismo , Femenino , Masculino , Ratones Endogámicos C57BL , Ratones Transgénicos , Parvalbúminas/metabolismoRESUMEN
Performance in several memory tasks is known to be unaffected by hippocampal damage sustained before learning, but is severely disrupted if the same damage occurs after learning. Memories for preferred locations, or home bases, in exploratory tasks can be formed by rats with hippocampal damage, but it is unknown if the memory for a home base survives hippocampal damage. To examine this question, for 30 min each day for five consecutive days, rats explored a circular open field containing one local cue. By Day 5 the rats preferentially went directly to that location, spent the majority of their time at that location, made rapid direct trips to that location when returning from an excursion and so demonstrated that the location was a home base. Memory for the cued location was examined after a 24 h or 14-day interval with the cue removed. In Experiments 1 and 2, control rats and rats with prior N-methyl-D-aspartic acid hippocampal lesions demonstrated memory of the home base location by making direct trips to that location. In Experiment 3, rats that had first explored the open field and cue and then received hippocampal lesions showed no memory for the cued location. The absence of anterograde impairment vs. the presence of retrograde impairment for memory of a spatial home base confirms a role for the hippocampus in the retention of spatial memory acquired during exploration.
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Amnesia Anterógrada/etiología , Amnesia Anterógrada/patología , Amnesia Retrógrada/etiología , Amnesia Retrógrada/patología , Daño Encefálico Crónico/etiología , Conducta Exploratoria/fisiología , Hipocampo/patología , Trastornos de la Memoria/fisiopatología , Animales , Daño Encefálico Crónico/inducido químicamente , Daño Encefálico Crónico/patología , Señales (Psicología) , Modelos Animales de Enfermedad , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/patología , Ratas , Ratas Sprague-Dawley , Ratas WistarRESUMEN
We present evidence that certain learning parameters can make a memory, even a very recent one, become independent of the hippocampus. We confirm earlier findings that damage to the hippocampus causes severe retrograde amnesia for context memories, but we show that repeated learning sessions create a context memory that is not vulnerable to the damage. The findings demonstrate that memories normally dependent on the hippocampus are incrementally strengthened in other memory networks with additional learning. The latter provides a new account for patterns of hippocampal retrograde amnesia and how memories may become independent of the hippocampus.
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Condicionamiento Clásico/fisiología , Hipocampo/fisiología , Memoria/fisiología , Análisis de Varianza , Animales , Conducta Animal/efectos de los fármacos , Condicionamiento Clásico/efectos de los fármacos , Aprendizaje Discriminativo/efectos de los fármacos , Electrochoque/efectos adversos , Agonistas de Aminoácidos Excitadores/toxicidad , Miedo/fisiología , Reacción Cataléptica de Congelación/efectos de los fármacos , Reacción Cataléptica de Congelación/fisiología , Hipocampo/lesiones , Masculino , N-Metilaspartato/toxicidad , RatasRESUMEN
Hippocampal place cells represent the cellular substrate of episodic memory. Place cell ensembles reorganize to support learning but must also maintain stable representations to facilitate memory recall. Despite extensive research, the learning-related role of place cell dynamics in health and disease remains elusive. Using chronic two-photon Ca2+ imaging in hippocampal area CA1 of wild-type and Df(16)A+/- mice, an animal model of 22q11.2 deletion syndrome, one of the most common genetic risk factors for cognitive dysfunction and schizophrenia, we found that goal-oriented learning in wild-type mice was supported by stable spatial maps and robust remapping of place fields toward the goal location. Df(16)A+/- mice showed a significant learning deficit accompanied by reduced spatial map stability and the absence of goal-directed place cell reorganization. These results expand our understanding of the hippocampal ensemble dynamics supporting cognitive flexibility and demonstrate their importance in a model of 22q11.2-associated cognitive dysfunction.
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Síndrome de DiGeorge/genética , Síndrome de DiGeorge/fisiopatología , Modelos Animales de Enfermedad , Hipocampo/fisiopatología , Aprendizaje/fisiología , Células de Lugar/fisiología , Animales , Femenino , Objetivos , Hipocampo/patología , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Células de Lugar/patología , Distribución AleatoriaRESUMEN
We present an overview of two of our on-going projects relating processes in the hippocampus to memory. We are trying to understand why retrograde amnesia occurs after damage to the hippocampus. Our experiments establish the generality of several new retrograde amnesia phenomena that are at odds with the consensus view of the role of the hippocampus in memory. We show in many memory tasks that complete damage to the hippocampus produces retrograde amnesia that is equivalent for recent and remote memories. Retrograde amnesia affects a much wider range of memory tasks than anterograde amnesia. Normal hippocampal processes can interfere with retention of a long-term memory stored outside the hippocampus. We conclude that the hippocampus competes with nonhippocampal systems during memory encoding and retrieval. Finally, we outline a project to understand and manipulate adult hippocampal neurogenesis in order to repair damaged hippocampal circuitry to recover lost cognitive functions.
Asunto(s)
Hipocampo/fisiología , Memoria/fisiología , Amnesia Retrógrada/patología , Humanos , Memoria/clasificaciónRESUMEN
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.