Associative and predictive hippocampal codes support memory-guided behaviors.

Episodic memory involves learning and recalling associations between items and their spatiotemporal context. Those memories can be further used to generate internal models of the world that enable predictions to be made. The mechanisms that support these associative and predictive aspects of memory are not yet understood.

Hippocampo-cortical circuits for selective memory encoding, routing, and replay.

Traditionally considered a homogeneous cell type, hippocampal pyramidal cells have been recently shown to be highly diverse. However, how this cellular diversity relates to the different hippocampal network computations that support memory-guided behavior is not yet known. We show that the anatomical identity of pyramidal cells is a major organizing principle of CA1 assembly dynamics, the emergence of memory replay, and cortical projection patterns in rats.

Hippocampal area CA2 controls seizure dynamics, interictal EEG abnormalities and social comorbidity in mouse models of temporal lobe epilepsy.

Unlabelled: Temporal lobe epilepsy (TLE) is characterized by spontaneous recurrent seizures, abnormal activity between seizures, and impaired behavior. CA2 pyramidal neurons (PNs) are potentially important because inhibiting them with a chemogenetic approach reduces seizure frequency in a mouse model of TLE. However, whether seizures could be stopped by timing inhibition just as a seizure begins is unclear.

CA2 orchestrates hippocampal network dynamics.

The hippocampus is composed of various subregions: CA1, CA2, CA3, and the dentate gyrus (DG). Despite the abundant hippocampal research literature, until recently, CA2 received little attention. The development of new genetic and physiological tools allowed recent studies characterizing the unique properties and functional roles of this hippocampal subregion.

Neuronal ensemble dynamics in social memory.

A large body of evidence suggests that cognitive functions rely on the coordination of ensembles of neurons across brain circuits. One example is social memory, the ability to recognize and remember other conspecifics. A broad range of brain regions have been implicated in social behaviors and memory processes.

CA2 physiology underlying social memory.

In recent years, convergent evidence has emerged in support of the idea of social brain networks, specific brain regions that are interconnected and support social behaviors. One of these regions is the CA2 area of the hippocampus, a small region strongly connected with cortical and subcortical areas implicated in social behaviors. Furthermore, CA2 area is enriched in receptors for several neuromodulators that are related to various aspects of social behaviors, suggesting that this area could be a key component of social information processing in the brain.

High-resolution optogenetics in space and time.

To understand the neural mechanisms of behavior, it is necessary to both monitor and perturb the activity of ensembles of neurons with high specificity. While neural ensemble recordings have been available for decades, progress in high-resolution manipulation techniques has lagged behind. Optogenetics has enabled the manipulation of genetically defined cell types in behaving animals, and recent developments, including multipoint nanofabricated light sources, provide spatiotemporal resolution on a par with that of physiological recordings.

Gamma rhythm communication between entorhinal cortex and dentate gyrus neuronal assemblies.

Gamma oscillations are thought to coordinate the spike timing of functionally specialized neuronal ensembles across brain regions. To test this hypothesis, we optogenetically perturbed gamma spike timing in the rat medial (MEC) and lateral (LEC) entorhinal cortices and found impairments in spatial and object learning tasks, respectively. MEC and LEC were synchronized with the hippocampal dentate gyrus through high- and low-gamma-frequency rhythms, respectively, and engaged either granule cells or mossy cells and CA3 pyramidal cells in a task-dependent manner.

Parallel Pathways for Mnemonic Processing.

In a recent study, Chen et al. showed that divergent subcortical-hippocampal projections are necessary for mnemonic processing. With a combination of elegant experiments, the authors revealed that, whereas a projection from the supramammillary nucleus (SuM) to dentate gyrus (DG) is needed for contextual memory, social memory requires the SuM-CA2 pathway.

Hippocampal CA2 sharp-wave ripples reactivate and promote social memory.

The consolidation of spatial memory depends on the reactivation ('replay') of hippocampal place cells that were active during recent behaviour. Such reactivation is observed during sharp-wave ripples (SWRs)-synchronous oscillatory electrical events that occur during non-rapid-eye-movement (non-REM) sleep and whose disruption impairs spatial memory. Although the hippocampus also encodes a wide range of non-spatial forms of declarative memory, it is not yet known whether SWRs are necessary for such memories.

Long-duration hippocampal sharp wave ripples improve memory.

Hippocampal sharp wave ripples (SPW-Rs) have been hypothesized as a mechanism for memory consolidation and action planning. The duration of ripples shows a skewed distribution with a minority of long-duration events. We discovered that long-duration ripples are increased in situations demanding memory in rats.

Proximodistal Organization of the CA2 Hippocampal Area.

The proximodistal axis is considered a major organizational principle of the hippocampus. At the interface between the hippocampus and other brain structures, CA2 apparently breaks this rule. The region is involved in social, temporal, and contextual memory function, but mechanisms remain elusive.

Origin of Gamma Frequency Power during Hippocampal Sharp-Wave Ripples.

Hippocampal sharp-wave ripples (SPW-Rs) support consolidation of recently acquired episodic memories and planning future actions by generating ordered neuronal sequences of previous or future experiences. SPW-Rs are characterized by several spectral components: a slow (5-15 Hz) sharp-wave, a high-frequency "ripple" oscillation (150-200 Hz), and a slow "gamma" oscillation (20-40 Hz). Using laminar hippocampal recordings and optogenetic manipulations, we dissected the origin of these spectral components.

A hippocampal circuit linking dorsal CA2 to ventral CA1 critical for social memory dynamics.

Recent results suggest that social memory requires the dorsal hippocampal CA2 region as well as a subset of ventral CA1 neurons. However, it is unclear whether dorsal CA2 and ventral CA1 represent parallel or sequential circuits. Moreover, because evidence implicating CA2 in social memory comes largely from long-term inactivation experiments, the dynamic role of CA2 in social memory remains unclear.

Direct effects of transcranial electric stimulation on brain circuits in rats and humans.

Transcranial electric stimulation is a non-invasive tool that can influence brain activity; however, the parameters necessary to affect local circuits in vivo remain to be explored. Here, we report that in rodents and human cadaver brains, ~75% of scalp-applied currents are attenuated by soft tissue and skull. Using intracellular and extracellular recordings in rats, we find that at least 1 mV/mm voltage gradient is necessary to affect neuronal spiking and subthreshold currents.

Entorhinal-CA3 Dual-Input Control of Spike Timing in the Hippocampus by Theta-Gamma Coupling.

Theta-gamma phase coupling and spike timing within theta oscillations are prominent features of the hippocampus and are often related to navigation and memory. However, the mechanisms that give rise to these relationships are not well understood. Using high spatial resolution electrophysiology, we investigated the influence of CA3 and entorhinal inputs on the timing of CA1 neurons.

Spatial coding and physiological properties of hippocampal neurons in the Cornu Ammonis subregions.

It is well-established that the feed-forward connected main hippocampal areas, CA3, CA2, and CA1 work cooperatively during spatial navigation and memory. These areas are similar in terms of the prevalent types of neurons; however, they display different spatial coding and oscillatory dynamics. Understanding the temporal dynamics of these operations requires simultaneous recordings from these regions.

Role of Hippocampal CA2 Region in Triggering Sharp-Wave Ripples.

Sharp-wave ripples (SPW-Rs) in the hippocampus are implied in memory consolidation, as shown by observational and interventional experiments. However, the mechanism of their generation remains unclear. Using two-dimensional silicon probe arrays, we investigated the propagation of SPW-Rs across the hippocampal CA1, CA2, and CA3 subregions.