Multi-regional control of amygdalar dynamics reliably reflects fear memory age.

The basolateral amygdala (BLA) is crucial for the encoding and expression of fear memory, yet it remains unexplored how neural activity in this region is dynamically influenced by distributed circuits across the brain to facilitate expression of fear memory of different ages. Using longitudinal multisite electrophysiological recordings in male mice, we find that the recall of older contextual fear memory is accompanied by weaker, yet more rhythmic, BLA gamma activity which is distally entrained by theta oscillations in both the hippocampal CA1 and the anterior cingulate cortex. Computational modeling with Light Gradient Boosting Machine using extracted oscillatory features from these three regions, as well as with Transformer using raw local field potentials, accurately classified remote from recent memory recall primarily based on BLA gamma and CA1 theta.

Central Role of Hypothalamic Circuits for Acupuncture's Anti-Parkinsonian Effects.

Despite clinical data stretching over millennia, the neurobiological basis of the effectiveness of acupuncture in treating diseases of the central nervous system has remained elusive. Here, using an established model of acupuncture treatment in Parkinson's disease (PD) model mice, we show that peripheral acupuncture stimulation activates hypothalamic melanin-concentrating hormone (MCH) neurons via nerve conduction. We further identify two separate neural pathways originating from anatomically and electrophysiologically distinct MCH neuronal subpopulations, projecting to the substantia nigra and hippocampus, respectively.

Silencing CA1 pyramidal cells output reveals the role of feedback inhibition in hippocampal oscillations.

The precise temporal coordination of neural activity is crucial for brain function. In the hippocampus, this precision is reflected in the oscillatory rhythms observed in CA1. While it is known that a balance between excitatory and inhibitory activity is necessary to generate and maintain these oscillations, the differential contribution of feedforward and feedback inhibition remains ambiguous.

From synapses to circuits: What mouse models have taught us about how autism spectrum disorder impacts hippocampal function.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that impacts a variety of cognitive and behavioral domains. While a genetic component of ASD has been well-established, none of the numerous syndromic genes identified in humans accounts for more than 1% of the clinical patients. Due to this large number of target genes, numerous mouse models of the disorder have been generated.

Silencing dentate newborn neurons alters excitatory/inhibitory balance and impairs behavioral inhibition and flexibility.

Adult neurogenesis confers the hippocampus with unparalleled neural plasticity, essential for intricate cognitive functions. The specific influence of sparse newborn neurons (NBNs) in modulating neural activities and subsequently steering behavior, however, remains obscure. Using an engineered NBN-tetanus toxin mouse model (NBN-TeTX), we noninvasively silenced NBNs, elucidating their crucial role in impulse inhibition and cognitive flexibility as evidenced through Morris water maze reversal learning and Go/Nogo task in operant learning.

A signal EMerGes from the noise.

In this issue of , Osanai et al. report an innovative approach to extract an electromyography (EMG) signal from multi-channel local field potential (LFP) recordings using independent component analysis (ICA). This ICA-based approach offers precise and stable long-term behavioral assessment, eliminating the need for direct muscular recordings.

An old model with new insights: endogenous retroviruses drive the evolvement toward ASD susceptibility and hijack transcription machinery during development.

The BTBR TItpr3/J (BTBR/J) strain is one of the most valid models of idiopathic autism, serving as a potent forward genetics tool to dissect the complexity of autism. We found that a sister strain with an intact corpus callosum, BTBR TF/ArtRbrc (BTBR/R), showed more prominent autism core symptoms but moderate ultrasonic communication/normal hippocampus-dependent memory, which may mimic autism in the high functioning spectrum. Intriguingly, disturbed epigenetic silencing mechanism leads to hyperactive endogenous retrovirus (ERV), a mobile genetic element of ancient retroviral infection, which increases de novo copy number variation (CNV) formation in the two BTBR strains.

Role of Calcr expressing neurons in the medial amygdala in social contact among females.

Social animals become stressed upon social isolation, proactively engaging in affiliative contacts among conspecifics after resocialization. We have previously reported that calcitonin receptor (Calcr) expressing neurons in the central part of the medial preoptic area (cMPOA) mediate contact-seeking behaviors in female mice. Calcr neurons in the posterodorsal part of the medial amygdala (MeApd) are also activated by resocialization, however their role in social affiliation is still unclear.

Behavioral status modulates CA2 influence on hippocampal network dynamics.

Dynamic interactions between the subregions of the hippocampus are required for the encoding and consolidation of memory. While the interplay and contributions of the CA1 and CA3 regions are well understood, we continue to learn more about how CA2 differentially contributes to the organization of network function. For example, CA2 place cells have been reported to be less spatially tuned during exploration, but uniquely capable of coding place while an animal stops.

The expanded circuitry of hippocampal ripples and replay.

The place cells and well-defined oscillatory population rhythms of the rodent hippocampus have served as a powerful model system in linking cells and circuits to memory function. While the initial three decades of place cell research primarily focused on the activity of neurons during exploration, the last twenty-five years have seen growing interest in the physiology of the hippocampus at rest. During slow-wave sleep and quiet wakefulness the hippocampus exhibits sharp-wave ripples (SWRs), short high-frequency, high-amplitude oscillations, that organize the reactivation or 'replay' of sequences of place cells, and interventions that disrupt SWRs impair learning.

Alterations in a cross-hemispheric circuit associates with novelty discrimination deficits in mouse models of neurodegeneration.

A major pathological hallmark of neurodegenerative diseases, including Alzheimer's, is a significant reduction in the white matter connecting the two cerebral hemispheres, as well as in the correlated activity between anatomically corresponding bilateral brain areas. However, the underlying circuit mechanisms and the cognitive relevance of cross-hemispheric (CH) communication remain poorly understood. Here, we show that novelty discrimination behavior activates CH neurons and enhances homotopic synchronized neural oscillations in the visual cortex.

A common epigenetic mechanism across different cellular origins underlies systemic immune dysregulation in an idiopathic autism mouse model.

Immune dysregulation plays a key role in the pathogenesis of autism. Changes occurring at the systemic level, from brain inflammation to disturbed innate/adaptive immune in the periphery, are frequently observed in patients with autism; however, the intrinsic mechanisms behind them remain elusive. We hypothesize a common etiology may lie in progenitors of different types underlying widespread immune dysregulation.

Behavioral and Cellular Tagging in Young and in Early Cognitive Aging.

The ability to maintain relevant information on a daily basis is negatively impacted by aging. However, the neuronal mechanism manifesting memory persistence in young animals and memory decline in early aging is not fully understood. A novel event, when introduced around encoding of an everyday memory task, can facilitate memory persistence in young age but not in early aging.

Amylin-Calcitonin receptor signaling in the medial preoptic area mediates affiliative social behaviors in female mice.

Social animals actively engage in contact with conspecifics and experience stress upon isolation. However, the neural mechanisms coordinating the sensing and seeking of social contacts are unclear. Here we report that amylin-calcitonin receptor (Calcr) signaling in the medial preoptic area (MPOA) mediates affiliative social contacts among adult female mice.

K efflux through postsynaptic NMDA receptors suppresses local astrocytic glutamate uptake.

Glutamatergic transmission prompts K efflux through postsynaptic NMDA receptors. The ensuing hotspot of extracellular K elevation depolarizes presynaptic terminal, boosting glutamate release, but whether this also affects glutamate uptake in local astroglia has remained an intriguing question. Here, we find that the pharmacological blockade, or conditional knockout, of postsynaptic NMDA receptors suppresses use-dependent increase in the amplitude and duration of the astrocytic glutamate transporter current (I ), whereas blocking astrocytic K channels prevents the duration increase only.

The impact of stress on the hippocampal spatial code.

Hippocampal function is severely compromised by prolonged, uncontrollable stress. However, how stress alters neural representations of our surroundings and events that occur within them remains less clear. We review hippocampal place cell studies that examine how spatial coding is affected by acute and chronic stress, as well as by stress accompanying fear conditioning.

Stepwise synaptic plasticity events drive the early phase of memory consolidation.

Memories are initially encoded in the hippocampus but subsequently consolidated to the cortex. Although synaptic plasticity is key to these processes, its precise spatiotemporal profile remains poorly understood. Using optogenetics to selectively erase long-term potentiation (LTP) within a defined temporal window, we found that distinct phases of synaptic plasticity play differential roles.

Lateralization of CA1 assemblies in the absence of CA3 input.

In the hippocampal circuit CA3 input plays a critical role in the organization of CA1 population activity, both during learning and sleep. While integrated spatial representations have been observed across the two hemispheres of CA1, these regions lack direct connectivity and thus the circuitry responsible remains largely unexplored. Here we investigate the role of CA3 in organizing bilateral CA1 activity by blocking synaptic transmission at CA3 terminals through the inducible transgenic expression of tetanus toxin.

CA2 inhibition reduces the precision of hippocampal assembly reactivation.

The structured reactivation of hippocampal neuronal ensembles during fast synchronous oscillatory events, termed sharp-wave ripples (SWRs), has been suggested to play a crucial role in the storage and use of memory. Activity in both the CA2 and CA3 subregions can precede this population activity in CA1, and chronic inhibition of either region alters SWR oscillations. However, the precise contribution of CA2 to the oscillation, as well as to the reactivation of CA1 neurons within it, remains unclear.

Differential Impact of Acute and Chronic Stress on CA1 Spatial Coding and Gamma Oscillations.

Chronic and acute stress differentially affect behavior as well as the structural integrity of the hippocampus, a key brain region involved in cognition and memory. However, it remains unclear if and how the facilitatory effects of acute stress on hippocampal information coding are disrupted as the stress becomes chronic. To examine this, we compared the impact of acute and chronic stress on neural activity in the CA1 subregion of male mice subjected to a chronic immobilization stress (CIS) paradigm.

Brain-specific heterozygous loss-of-function of ATP2A2, endoplasmic reticulum Ca2+ pump responsible for Darier's disease, causes behavioral abnormalities and a hyper-dopaminergic state.

A report of a family of Darier's disease with mood disorders drew attention when the causative gene was identified as ATP2A2 (or SERCA2), which encodes a Ca2+ pump on the endoplasmic reticulum (ER) membrane and is important for intracellular Ca2+ signaling. Recently, it was found that loss-of-function mutations of ATP2A2 confer a risk of neuropsychiatric disorders including depression, bipolar disorder and schizophrenia. In addition, a genome-wide association study found an association between ATP2A2 and schizophrenia.

Calcitonin receptor signaling in the medial preoptic area enables risk-taking maternal care.

Maternal mammals exhibit heightened motivation to care for offspring, but the underlying neuromolecular mechanisms have yet to be clarified. Here, we report that the calcitonin receptor (Calcr) and its ligand amylin are expressed in distinct neuronal populations in the medial preoptic area (MPOA) and are upregulated in mothers. Calcr+ MPOA neurons activated by parental care project to somatomotor and monoaminergic brainstem nuclei.

Local circuit allowing hypothalamic control of hippocampal area CA2 activity and consequences for CA1.

The hippocampus is critical for memory formation. The hypothalamic supramammillary nucleus (SuM) sends long-range projections to hippocampal area CA2. While the SuM-CA2 connection is critical for social memory, how this input acts on the local circuit is unknown.