Propagation of sharp wave-ripple activity in the mouse hippocampal CA3 subfield in vitro.

Sharp wave-ripple complexes (SPW-Rs) are spontaneous oscillatory events that characterize hippocampal activity during resting periods and slow-wave sleep. SPW-Rs are related to memory consolidation - the process during which newly acquired memories are transformed into long-lasting memory traces. To test the involvement of SPW-Rs in this process, it is crucial to understand how SPW-Rs originate and propagate throughout the hippocampus.

Hippocampal GABAergic interneurons and memory.

One of the most captivating questions in neuroscience revolves around the brain's ability to efficiently and durably capture and store information. It must process continuous input from sensory organs while also encoding memories that can persist throughout a lifetime. What are the cellular-, subcellular-, and network-level mechanisms that underlie this remarkable capacity for long-term information storage? Furthermore, what contributions do distinct types of GABAergic interneurons make to this process? As the hippocampus plays a pivotal role in memory, our review focuses on three aspects: (1) delineation of hippocampal interneuron types and their connectivity, (2) interneuron plasticity, and (3) activity patterns of interneurons during memory-related rhythms, including the role of long-range interneurons and disinhibition.

Temperature elevations can induce switches to homoclinic action potentials that alter neural encoding and synchronization.

Almost seventy years after the discovery of the mechanisms of action potential generation, some aspects of their computational consequences are still not fully understood. Based on mathematical modeling, we here explore a type of action potential dynamics - arising from a saddle-node homoclinic orbit bifurcation - that so far has received little attention. We show that this type of dynamics is to be expected by specific changes in common physiological parameters, like an elevation of temperature.

Interneuron switching on and off across memory rhythms.

In this issue of Neuron, Szabo et al. uncover a unique subtype of interneurons that is highly active during ripples but largely silent during theta oscillations. The study provides exciting new insights into the regulation and propagation of ripples in CA1 and beyond.

In vitro and in vivo anti-epileptic efficacy of eslicarbazepine acetate in a mouse model of KCNQ2-related self-limited epilepsy.

Background And Purpose: The KCNQ2 gene encodes for the K 7.2 subunit of non-inactivating potassium channels. KCNQ2-related diseases range from autosomal dominant neonatal self-limited epilepsy, often caused by KCNQ2 haploinsufficiency, to severe encephalopathies caused by KCNQ2 missense variants.

Subiculum as a generator of sharp wave-ripples in the rodent hippocampus.

Sharp wave-ripples (SWRs) represent synchronous discharges of hippocampal neurons and are believed to play a major role in memory consolidation. A large body of evidence suggests that SWRs are exclusively generated in the CA3-CA2 network. In contrast, here, we provide several lines of evidence showing that the subiculum can function as a secondary SWRs generator.

Generation of Sharp Wave-Ripple Events by Disinhibition.

Sharp wave-ripple complexes (SWRs) are hippocampal network phenomena involved in memory consolidation. To date, the mechanisms underlying their occurrence remain obscure. Here, we show how the interactions between pyramidal cells, parvalbumin-positive (PV) basket cells, and an unidentified class of anti-SWR interneurons can contribute to the initiation and termination of SWRs.

Spermidine protects from age-related synaptic alterations at hippocampal mossy fiber-CA3 synapses.

Aging is associated with functional alterations of synapses thought to contribute to age-dependent memory impairment (AMI). While therapeutic avenues to protect from AMI are largely elusive, supplementation of spermidine, a polyamine normally declining with age, has been shown to restore defective proteostasis and to protect from AMI in Drosophila. Here we demonstrate that dietary spermidine protects from age-related synaptic alterations at hippocampal mossy fiber (MF)-CA3 synapses and prevents the aging-induced loss of neuronal mitochondria.

Could electrical coupling contribute to the formation of cell assemblies?

Cell assemblies and central pattern generators (CPGs) are related types of neuronal networks: both consist of interacting groups of neurons whose collective activities lead to defined functional outputs. In the case of a cell assembly, the functional output may be interpreted as a representation of something in the world, external or internal; for a CPG, the output 'drives' an observable (i.e.

Involvement of Mossy Cells in Sharp Wave-Ripple Activity In Vitro.

The role of mossy cells (MCs) of the hippocampal dentate area has long remained mysterious. Recent research has begun to unveil their significance in spatial computation of the hippocampus. Here, we used an in vitro model of sharp wave-ripple complexes (SWRs), which contribute to hippocampal memory formation, to investigate MC involvement in this fundamental population activity.

Hippocampal Ripple Oscillations and Inhibition-First Network Models: Frequency Dynamics and Response to GABA Modulators.

Hippocampal ripples are involved in memory consolidation, but the mechanisms underlying their generation remain unclear. Models relying on interneuron networks in the CA1 region disagree on the predominant source of excitation to interneurons: either "direct," via the Schaffer collaterals that provide feedforward input from CA3 to CA1, or "indirect," via the local pyramidal cells in CA1, which are embedded in a recurrent excitatory-inhibitory network. Here, we used physiologically constrained computational models of basket-cell networks to investigate how they respond to different conditions of transient, noisy excitation.

Excitatory Microcircuits within Superficial Layers of the Medial Entorhinal Cortex.

The distinctive firing pattern of grid cells in the medial entorhinal cortex (MEC) supports its role in the representation of space. It is widely believed that the hexagonal firing field of grid cells emerges from neural dynamics that depend on the local microcircuitry. However, local networks within the MEC are still not sufficiently characterized.

Human cerebrospinal fluid monoclonal N-methyl-D-aspartate receptor autoantibodies are sufficient for encephalitis pathogenesis.

SEE ZEKERIDOU AND LENNON DOI101093/AWW213 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a recently discovered autoimmune syndrome associated with psychosis, dyskinesias, and seizures. Little is known about the cerebrospinal fluid autoantibody repertoire. Antibodies against the NR1 subunit of the NMDAR are thought to be pathogenic; however, direct proof is lacking as previous experiments could not distinguish the contribution of further anti-neuronal antibodies.

Functional Diversity of Subicular Principal Cells during Hippocampal Ripples.

Unlabelled: Cortical and hippocampal oscillations play a crucial role in the encoding, consolidation, and retrieval of memory. Sharp-wave associated ripples have been shown to be necessary for the consolidation of memory. During consolidation, information is transferred from the hippocampus to the neocortex.

KCNQ5 K(+) channels control hippocampal synaptic inhibition and fast network oscillations.

KCNQ2 (Kv7.2) and KCNQ3 (Kv7.3) K(+) channels dampen neuronal excitability and their functional impairment may lead to epilepsy.

Recruitment of oriens-lacunosum-moleculare interneurons during hippocampal ripples.

Sharp wave-associated ∼200-Hz ripple oscillations in the hippocampus have been implicated in the consolidation of memories. However, knowledge on mechanisms underlying ripples is still scarce, in particular with respect to synaptic involvement of specific cell types. Here, we used cell-attached and whole-cell recordings in vitro to study activity of pyramidal cells and oriens-lacunosum-moleculare (O-LM) interneurons during ripples.

Axonal properties determine somatic firing in a model of in vitro CA1 hippocampal sharp wave/ripples and persistent gamma oscillations.

Evidence has been presented that CA1 pyramidal cells, during spontaneous in vitro sharp wave/ripple (SPW-R) complexes, generate somatic action potentials that originate in axons. 'Participating' (somatically firing) pyramidal cells fire (almost always) at most once during a particular SPW-R whereas non-participating cells virtually never fire during an SPW-R. Somatic spikelets were small or absent, while ripple-frequency EPSCs and IPSCs occurred during the SPW-R in pyramidal neurons.

Coherent phasic excitation during hippocampal ripples.

High-frequency hippocampal network oscillations, or "ripples," are thought to be involved in episodic memory. According to current theories, memory traces are represented by assemblies of principal neurons that are activated during ripple-associated network states. Here we performed in vivo and in vitro experiments to investigate the synaptic mechanisms during ripples.

Cannabinoids disrupt hippocampal sharp wave-ripples via inhibition of glutamate release.

Cannabis consumption results in impaired learning. The proper synchronization of neuronal activity in the mammalian hippocampus gives rise to network rhythms that are implicated in memory formation. Here, we have studied the impact of cannabinoids on hippocampal sharp waves and associated ripple oscillations using field- and whole-cell voltage-clamp recordings.

Cellular correlate of assembly formation in oscillating hippocampal networks in vitro.

Neurons form transiently stable assemblies that may underlie cognitive functions, including memory formation. In most brain regions, coherent activity is organized by network oscillations that involve sparse firing within a well-defined minority of cells. Despite extensive work on the underlying cellular mechanisms, a fundamental question remains unsolved: how are participating neurons distinguished from the majority of nonparticipators? We used physiological and modeling techniques to analyze neuronal activity in mouse hippocampal slices during spontaneously occurring high-frequency network oscillations.

Muskelin regulates actin filament- and microtubule-based GABA(A) receptor transport in neurons.

Intracellular transport regulates protein turnover including endocytosis. Because of the spatial segregation of F-actin and microtubules, internalized cargo vesicles need to employ myosin and dynein motors to traverse both cytoskeletal compartments. Factors specifying cargo delivery across both tracks remain unknown.

GluK1 inhibits calcium dependent and independent transmitter release at associational/commissural synapses in area CA3 of the hippocampus.

CA3 pyramidal cells receive three main excitatory inputs: the first one is the mossy fiber input, synapsing mainly on the proximal apical dendrites. Second, entorhinal cortex cells form excitatory connections with CA3 pyramidal cells via the perforant path in the stratum lacunosum moleculare. The third input involves the ipsi-and contralateral connections, termed the associational/commissural (A/C) pathway terminating in the stratum radiatum of CA3, thus forming a feedback loop within this region.

Synaptic PRG-1 modulates excitatory transmission via lipid phosphate-mediated signaling.

Plasticity related gene-1 (PRG-1) is a brain-specific membrane protein related to lipid phosphate phosphatases, which acts in the hippocampus specifically at the excitatory synapse terminating on glutamatergic neurons. Deletion of prg-1 in mice leads to epileptic seizures and augmentation of EPSCs, but not IPSCs. In utero electroporation of PRG-1 into deficient animals revealed that PRG-1 modulates excitation at the synaptic junction.

An approach for reliably investigating hippocampal sharp wave-ripples in vitro.

Background: Among the various hippocampal network patterns, sharp wave-ripples (SPW-R) are currently the mechanistically least understood. Although accurate information on synaptic interactions between the participating neurons is essential for comprehensive understanding of the network function during complex activities like SPW-R, such knowledge is currently notably scarce.

Methodology/principal Findings: We demonstrate an in vitro approach to SPW-R that offers a simple experimental tool allowing detailed analysis of mechanisms governing the sharp wave-state of the hippocampus.

Differential cAMP signaling at hippocampal output synapses.

cAMP is a critical second messenger involved in synaptic transmission and synaptic plasticity. Here, we show that activation of the adenylyl cyclase by forskolin and application of the cAMP-analog Sp-5,6-DCl-cBIMPS both mimicked and occluded tetanus-induced long-term potentiation (LTP) in subicular bursting neurons, but not in subicular regular firing cells. Furthermore, LTP in bursting cells was inhibited by protein kinase A (PKA) inhibitors Rp-8-CPT-cAMP and H-89.