Episodic Aspects of a Path Navigated Through Hippocampal Neurobiology.

As requested by the editors of this special issue of Hippocampus on Scientific Histories of Hippocampal Research, this review provides a detailed personal perspective and historical background on the research involved in a number of findings. The review includes description of the development of the water maze and its use in providing evidence to support the role of the hippocampus in spatial memory function. The review also describes how the water maze was then used in further work to support the proposal that NMDA-dependent synaptic modification in the hippocampus mediates the encoding of new spatial memories.

Brain and cognitive changes in patients with long COVID compared with infection-recovered control subjects.

Between 2.5% and 28% of people infected with SARS-CoV-2 suffer long COVID or persistence of symptoms for months after acute illness. Many symptoms are neurological, but the brain changes underlying the neuropsychological impairments remain unclear.

Cell-type-specific optogenetic stimulation of the locus coeruleus induces slow-onset potentiation and enhances everyday memory in rats.

Memory formation is typically divided into phases associated with encoding, storage, consolidation, and retrieval. The neural determinants of these phases are thought to differ. This study first investigated the impact of the experience of novelty in rats incurred at a different time, before or after, the precise moment of memory encoding.

Execution of new trajectories toward a stable goal without a functional hippocampus.

The hippocampus is a critical component of a mammalian spatial navigation system, with the firing sequences of hippocampal place cells during sleep or immobility constituting a "replay" of an animal's past trajectories. A novel spatial navigation task recently revealed that such "replay" sequences of place fields can also prospectively map onto imminent new paths to a goal that occupies a stable location during each session. It was hypothesized that such "prospective replay" sequences may play a causal role in goal-directed navigation.

Neuronal signature of spatial decision-making during navigation by freely moving rats by using calcium imaging.

A challenge in spatial memory is understanding how place cell firing contributes to decision-making in navigation. A spatial recency task was created in which freely moving rats first became familiar with a spatial context over several days and thereafter were required to encode and then selectively recall one of three specific locations within it that was chosen to be rewarded that day. Calcium imaging was used to record from more than 1,000 cells in area CA1 of the hippocampus of five rats during the exploration, sample, and choice phases of the daily task.

Sleep deprivation and hippocampal ripple disruption after one-session learning eliminate memory expression the next day.

Memory reactivation during non-rapid-eye-movement ripples is thought to communicate new information to a systems-wide network and thus can be a key player mediating the positive effect of sleep on memory consolidation. Causal experiments disrupting ripples have only been performed in multiday training paradigms, which decrease but do not eliminate memory performance, and no comparison with sleep deprivation has been made. To enable such investigations, we developed a one-session learning paradigm in a Plusmaze and show that disruption of either sleep with gentle handling or hippocampal ripples with electrical stimulation impaired long-term memory.

Ca2+ imaging of self and other in medial prefrontal cortex during social dominance interactions in a tube test.

The study of social dominance interactions between animals offers a window onto the decision-making involved in establishing dominance hierarchies and an opportunity to examine changes in social behavior observed in certain neurogenetic disorders. Competitive social interactions, such as in the widely used tube test, reflect this decision-making. Previous studies have focused on the different patterns of behavior seen in the dominant and submissive animal, neural correlates of effortful behavior believed to mediate the outcome of such encounters, and interbrain correlations of neural activity.

Brain region networks for the assimilation of new associative memory into a schema.

Alterations in long-range functional connectivity between distinct brain regions are thought to contribute to the encoding of memory. However, little is known about how the activation of an existing network of neocortical and hippocampal regions might support the assimilation of relevant new information into the preexisting knowledge structure or 'schema'. Using functional mapping for expression of plasticity-related immediate early gene products, we sought to identify the long-range functional network of paired-associate memory, and the encoding and assimilation of relevant new paired-associates.

Distinct contributions of ventral CA1/amygdala co-activation to the induction and maintenance of synaptic plasticity.

The amygdala is known to modulate hippocampal synaptic plasticity. One role could be an immediate effect of basolateral amygdala (BLA) in priming synaptic plasticity in the hippocampus. Another role could be through associative synaptic co-operation and competition that triggers events involved in the maintenance of synaptic potentiation.

A Behavioral Task Modeling 'Everyday Memory' in an Event Arena to Foster Allocentric Representations for Rodents.

The event arena provides an optimal platform to investigate learning and memory. The appetitive everyday memory task described in this paper provides a robust protocol for the investigation of episodic and spatial memory in rodents, which specifically fosters allocentric memory representation. Rats are trained to find and dig for food during the encoding phase and, after a time delay, rats are given a choice to find the reward food pellet in the correct location.

Experiential modulation of social dominance in a SYNGAP1 rat model of Autism Spectrum Disorders.

Advances in the understanding of developmental brain disorders such as autism spectrum disorders (ASDs) are being achieved through human neurogenetics such as, for example, identifying de novo mutations in SYNGAP1 as one relatively common cause of ASD. A recently developed rat line lacking the calcium/lipid binding (C2) and GTPase activation protein (GAP) domain may further help uncover the neurobiological basis of deficits in children with ASD. This study focused on social dominance in the tube test using Syngap (rats heterozygous for the C2/GAP domain deletion) as alterations in social behaviour are a key facet of the human phenotype.

iHELMET: A 3D-printing solution for safe endoscopic Ca recording in social neuroscience.

Background: In vivo calcium imaging using a microendoscope is a state-of-the-art technique to study the cellular activity inside the brain of freely moving animals such as mice or rats. A problem that can arise in social behaviour tests in rats, or similar size rodents, is that one animal interferes with or may even damage the miniature endoscopic camera attached to the second animal.

New Method: We outline an inexpensive, lightweight, 3D-printed protector (iHELMET) that surrounds but is not in physical contact with the camera, together with details of its design and construction.

A stable home-base promotes allocentric memory representations of episodic-like everyday spatial memory.

A key issue in neurobiological studies of episodic-like memory is the geometric frame of reference in which memory traces of experience are stored. Assumptions are sometimes made that specific protocols favour either allocentric (map-like) or egocentric (body-centred) representations. There are, however, grounds for suspecting substantial ambiguity about coding strategy, including the necessity to use both frames of reference occasionally, but tests of memory representation are not routinely conducted.

Frontal and Insular Input to the Dorsolateral Temporal Pole in Primates: Implications for Auditory Memory.

The temporal pole (TP) has been involved in multiple functions from emotional and social behavior, semantic processing, memory, language in humans and epilepsy surgery, to the fronto-temporal neurodegenerative disorder (semantic) dementia. However, the role of the TP subdivisions is still unclear, in part due to the lack of quantitative data about TP connectivity. This study focuses in the dorsolateral subdivision of the TP: area 38.

In memoriam: John Lisman - commentaries on CaMKII as a memory molecule.

Shortly before he died in October 2017, John Lisman submitted an invited review to Molecular Brain on 'Criteria for identifying the molecular basis of the engram (CaMKII, PKMζ)'. John had no opportunity to read the referees' comments, and as a mark of the regard in which he was held by the neuroscience community the Editors decided to publish his review as submitted. This obituary takes the form of a series of commentaries on Lisman's review.

Silent Learning.

We introduce the concept of "silent learning"-the capacity to learn despite neuronal cell-firing being largely absent. This idea emerged from thinking about dendritic computation [1, 2] and examining whether the encoding, expression, and retrieval of hippocampal-dependent memory could be dissociated using the intrahippocampal infusion of pharmacological compounds. We observed that very modest enhancement of GABAergic inhibition with low-dose muscimol blocked both cell-firing and the retrieval of an already-formed memory but left induction of long-term potentiation (LTP) and new spatial memory encoding intact (silent learning).

Memory, Novelty and Prior Knowledge.

Over the 40 years that TINS has been in existence, there has been substantial progress in understanding the types, organisation, and neural mechanisms of memory. The selectivity of memory maintenance and retention remains a puzzle, and we here summarise two contributions of our own research to this enigma: the striking impact of the novelty and surprise often of other events happening around the time that a new memory is encoded and how activated prior knowledge guides the updating process that characterises aspects of memory consolidation.

Memory: Looking back and looking forward.

This review brings together past and present achievements in memory research, ranging from molecular to psychological discoveries. Despite some false starts, major advances include our growing understanding of learning-related neural plasticity and the characterisation of different classes of memory. One striking example is the ability to reactivate targeted neuronal ensembles so that an animal will seemingly re-experience a particular memory, with the further potential to modify such memories.

Angular Gyrus Involvement at Encoding and Retrieval Is Associated with Durable But Less Specific Memories.

After consolidation, information belonging to a mental schema is better remembered, but such memory can be less specific when it comes to details. A neuronal mechanism consistent with this behavioral pattern could result from a dynamic interaction that entails mediation by a specific cortical network with associated hippocampal disengagement. We now report that, in male and female adult human subjects, encoding and later consolidation of a series of objects embedded in a semantic schema was associated with a buildup of activity in the angular gyrus (AG) that predicted memory 24 h later.

Everyday memory: towards a translationally effective method of modelling the encoding, forgetting and enhancement of memory.

The testing of cognitive enhancers could benefit from the development of novel behavioural tasks that display better translational relevance for daily memory and permit the examination of potential targets in a within-subjects manner with less variability. We here outline an optimized spatial 'everyday memory' task. We calibrate it systematically by interrogating certain well-established determinants of memory and consider its potential for revealing novel features of encoding-related gene activation.

The Kinase Function of MSK1 Regulates BDNF Signaling to CREB and Basal Synaptic Transmission, But Is Not Required for Hippocampal Long-Term Potentiation or Spatial Memory.

The later stages of long-term potentiation (LTP) and spatial memory are believed to depend upon gene transcription. Accordingly, considerable attempts have been made to identify both the mechanisms by which transcription is regulated and indeed the gene products themselves. Previous studies have shown that deletion of one regulator of transcription, the mitogen- and stress-activated kinase 1 (MSK1), causes an impairment of spatial memory.

The Yin and Yang of Memory Consolidation: Hippocampal and Neocortical.

While hippocampal and cortical mechanisms of memory consolidation have long been studied, their interaction is poorly understood. We sought to investigate potential interactions with respect to trace dominance, strengthening, and interference associated with postencoding novelty or sleep. A learning procedure was scheduled in a watermaze that placed the impact of novelty and sleep in opposition.

Transient medial prefrontal perturbation reduces false memory formation.

Knowledge extracted across previous experiences, or schemas, benefit encoding and retention of congruent information. However, they can also reduce specificity and augment memory for semantically related, but false information. A demonstration of the latter is given by the Deese-Roediger-McDermott (DRM) paradigm, where the studying of words that fit a common semantic schema are found to induce false memories for words that are congruent with the given schema, but were not studied.