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Play behavior has been extensively studied across species, but its direct role in social relationships remains unclear. Here we use an "isolation versus separation" protocol to identify behaviors associated with relationship renewal in adolescent female rats. Members of a dyad that had been separated for 24 hr, without isolation from other peers, initially increased investigative behaviors relative to nonseparated peers; however, in contrast with social isolation, separation by itself did not increase rough-and-tumble play. The data suggest that increased play following isolation depends on general motivations, rather than a "peer-specific" drive to renew relationships with an individual. This is consistent with a role of play in more general social learning rather than reestablishing bonds or expectations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Across systems, higher-order interactions between components govern emergent dynamics. Here we tested whether contextual threat memory retrieval in mice relies on higher-order interactions between dorsal CA1 hippocampal neurons requiring learning-induced dendritic spine plasticity. We compared population-level Ca2 + transients as wild-type mice (with intact learning-induced spine plasticity and memory) and amnestic mice (TgCRND8 mice with high levels of amyloid-β and deficits in learning-induced spine plasticity and memory) were tested for memory. Using machine-learning classifiers with different capacities to use input data with complex interactions, our findings indicate complex neuronal interactions in the memory representation of wild-type, but not amnestic, mice. Moreover, a peptide that partially restored learning-induced spine plasticity also restored the statistical complexity of the memory representation and memory behavior in Tg mice. These findings provide a previously missing bridge between levels of analysis in memory research, linking receptors, spines, higher-order neuronal dynamics and behavior., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Degus ( Octodon degus ) are a highly gregarious species of caviomorph rodent native to South America. Kinship does not appear to play a role in degu social structure, and alloparenting is often observed between unrelated females. We hypothesize that female degus readily establish new, cooperative peer relationships. Here we examined changes in dyadic behavior as individuals became more familiar, testing the prediction that interactions between female strangers would quickly resemble those of cagemates. Adult degus underwent a several week series of 20 minute "reunion" social exposures, interleaving reunions with initial strangers and, as a control, familiar cagemates. Males showed initially higher levels of interaction with strangers that converged with cagemate levels over experience. Females could be split into two groups: those that consistently interacted more with strangers (SC-HIGH) and those that did not (SC-LOW); however, unlike males, the higher interaction levels observed between strangers did not change with familiarity. Following 10 reunion sessions female strangers were housed together to create "new cagemates". Even after co-housing, SC-HIGH (but not SC-LOW) females continued to interact more with the relatively unfamiliar peer than their prior cagemate, particularly in face-to-face and rear-sniffing interactions. A final set of reunions with new strangers found that individual differences in female responses to social novelty were preserved. These results reveal sex differences in the rules relating familiarization to social relationships in degus, and that female predispositions toward cooperation may be due to inherent responses to new individuals more than to how they negotiate relationships over time., Competing Interests: Competing interest statement: authors declare that they have no competing interests with this work.

Maturation of the forebrain involves transitions from higher to lower levels of synaptic plasticity. The timecourse of these changes likely differs between regions, with the stabilization of some networks scaffolding the development of others. To gain better insight into neuroplasticity changes associated with maturation to adulthood, we examined the distribution of two molecular markers for developmental plasticity. We conducted the examination on male and female degus ( Octodon degus ), a rodent species with a relatively long developmental timecourse that offers a promising model for studying both development and age-related neuropathology. Immunofluorescent staining was used to measure perineuronal nets (PNNs), an extracellular matrix structure that emerges during the closure of critical plasticity periods, as well as microglia, resident immune cells that play a crucial role in synapse remodeling during development. PNNs (putatively restricting plasticity) were found to be higher in non-juvenile (>3 month) degus, while levels of microglia (putatively mediating plasticity) decreased across ages more gradually, and with varying timecourses between regions. Degus also showed notable variation in PNN levels between cortical layers and hippocampal subdivisions that have not been previously reported in other species. These results offer a glimpse into neuroplasticity changes occurring during degu maturation and highlight adolescence as a unique phase of neuroplasticity, in which PNNs have been established but microglia remain relatively high., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Garduño, Hanni, Hays, Cogram, Insel and Xu.)

Many animals become more motivated to interact after a period of isolation. This phenomenon may involve general drives, e.g. for social touch or companionship, as well as drives that are specific to particular peers, and which ultimately serve to reestablish relationships between the individuals. Female degus are known to be affiliative with multiple other individuals, including unrelated and unfamiliar conspecifics, offering an opportunity to study social motivation independent from exclusive pair-bonds or overt, same-sex competition. We attempted to disentangle factors driving peer interaction by examining reunion behavior across several social isolation and separation manipulations. High levels of interaction were observed between adult females who had been separated even without isolation, revealing a drive to re-establish relationships with specific peers. The content of separation-only reunions differed from isolation, with the latter involving more early-session interaction, higher levels of allogrooming before rear-sniffing, and a higher ratio of chitter vocalizations. To assess whether post-isolation behavior was related to stress, we examined reunions following a non-social (footshock) stressor. Like isolation, footshock increased early-session interactions, but did not increase allogrooming before rear-sniffing or chittering, as compared with controls. To test whether separation-only reunion behavior shared qualities with relationship formation, we also examined reunions of new (stranger) dyads. Strangers exhibited higher levels of interaction than cagemates, with particularly high levels of late-session rear-sniffing. Like separation-only reunions, strangers showed more non-chitter vocalizations and lower levels of allogrooming before rear-sniffing. Across experiments, an exploratory clustering method was used to identify vocalizations that differed between conditions. This yielded promising leads for future investigation, including a chaff-type syllable that may have been more common during relationship renewal. Overall, results are consistent with the hypothesis that female degu reunions are supported by both general and peer-stimulus specific drives, expressed through the structure of physical and vocal interactions over time., Competing Interests: The authors have declared that no competing interests exist.

Group-living animals vary in social behavior across multiple dimensions, including in the selectivity of social interactions with familiar versus unfamiliar peers. Standardized behavioral tests can be used to tease apart different dimensions of behavior. These serve a dual function-on one hand, helping to isolate behavioral factors that may support collective behavior in natural habitats, and, on another, providing a basis for comparative approaches to understanding physiological mechanisms of behavior. Degus (Octodon degus) are South American caviomorph rodents that nest and forage in groups with relatively low genetic relatedness. Flexibility in group membership is likely supported by gregariousness toward strangers, but the relative preference for strangers compared with familiar individuals has not been systematically tested. We assessed the specificity of social preferences in female degus using a same-sex partner preference test. Degus huddled extensively with both familiar and unfamiliar peers, with no average preference for one over the other. Detailed analysis of social interactions demonstrated an effect of familiarity on social investigation and aggressive behaviors, indicating that degus distinguished between familiar and unfamiliar conspecifics, even though it did not impact huddling. This behavioral profile is thus far unique to degus; in similar tests, meadow and prairie voles exhibit strong partner preferences for known peers, while mice exhibit low social huddling and spend relatively less time in social chambers. Understanding how group-living species differ in specific aspects of social behavior such as familiarity/novelty preference and propensity for social contact will offer a foundation to interpret differences in neural systems supporting sociality., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Symptoms of schizophrenia may arise from a failure of cortical circuits to filter-out irrelevant inputs. Schizophrenia has also been linked to disruptions in cortical inhibitory interneurons, consistent with the possibility that in the normally functioning brain, these cells are in some part responsible for determining which sensory inputs are relevant versus irrelevant. Here, we develop a neural network model that demonstrates how the cortex may learn to ignore irrelevant inputs through plasticity processes affecting inhibition. The model is based on the proposal that the amount of excitatory output from a cortical circuit encodes the expected magnitude of reward or punishment ("relevance"), which can be trained using a temporal difference learning mechanism acting on feedforward inputs to inhibitory interneurons. In the model, irrelevant and blocked stimuli drive lower levels of excitatory activity compared with novel and relevant stimuli, and this difference in activity levels is lost following disruptions to inhibitory units. When excitatory units are connected to a competitive-learning output layer with a threshold, the relevance code can be shown to "gate" both learning and behavioral responses to irrelevant stimuli. Accordingly, the combined network is capable of recapitulating published experimental data linking inhibition in frontal cortex with fear learning and expression. Finally, the model demonstrates how relevance learning can take place in parallel with other types of learning, through plasticity rules involving inhibitory and excitatory components, respectively. Altogether, this work offers a theory of how the cortex learns to selectively inhibit inputs, providing insight into how relevance-assignment problems may emerge in schizophrenia., Competing Interests: The authors have declared that no competing interests exist.

Some animals learn to fear a situation after observing another individual come to harm, and this learning is influenced by the animals' social relationship and history. An important but sometimes overlooked factor in studies of observational fear learning is that social context not only affects observers, but may also influence the behavior and communications expressed by those being observed. Here we sought to investigate whether observational fear learning in the degu (Octodon degus) is affected by social familiarity, and the degree to which vocal expressions of alarm or distress contribute. 'Demonstrator' degus underwent contextual fear conditioning in the presence of a cagemate or stranger observer. Among the 15 male pairs, observers of familiar demonstrators exhibited higher freezing rates than observers of strangers when returned to the conditioning environment one day later. Observer freezing during testing was, however, also related to the proportion of short- versus long- inter-call-intervals (ICIs) in vocalizations recorded during prior conditioning. In a regression model that included both social relationship and ICI patterns, only the latter was significant. Further investigation of vocalizations, including use of a novel, directed k-means clustering approach, suggested that temporal structure rather than tonal variations may have been responsible for communicating danger. These data offer insight into how different expressions of distress or fear may impact an observer, adding to the complexity of social context effects in studies of empathy and social cognition. The experiments also offer new data on degu alarm calls and a potentially novel methodological approach to complex vocalizations., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The lateral entorhinal cortex (LEC) is thought to bind sensory events with the environment where they took place. To compare the relative influence of transient events and temporally stable environmental stimuli on the firing of LEC cells, we recorded neuron spiking patterns in the region during blocks of a trace eyeblink conditioning paradigm performed in two environments and with different conditioning stimuli. Firing rates of some neurons were phasically selective for conditioned stimuli in a way that depended on which room the rat was in; nearly all neurons were tonically selective for environments in a way that depended on which stimuli had been presented in those environments. As rats moved from one environment to another, tonic neuron ensemble activity exhibited prospective information about the conditioned stimulus associated with the environment. Thus, the LEC formed phasic and tonic codes for event-environment associations, thereby accurately differentiating multiple experiences with overlapping features.

Memories for recent experiences are rich in incidental detail, but with time the brain is thought to extract latent rules and structures common across past experiences. We show that over weeks following the acquisition of two distinct associative memories, neuron firing in the rat prelimbic prefrontal cortex (mPFC) became less selective for perceptual features unique to each association and, with an apparently different time-course, became more selective for common relational features. We further found that during exposure to a novel experimental context, memory expression and neuron selectivity for relational features immediately generalized to the new situation. These neural patterns offer a window into the network-level processes by which the mPFC develops a knowledge structure of the world that can be adaptively applied to new experiences., Competing Interests: The authors declare that no competing interests exist.

The dentate gyrus (DG) is important for encoding contextual memories, but little is known about how a population of DG neurons comes to encode and support a particular memory. One possibility is that recruitment into an engram depends on a neuron's excitability. Here, we manipulated excitability by overexpressing CREB in a random population of DG neurons and examined whether this biased their recruitment to an engram supporting a contextual fear memory. To directly assess whether neurons overexpressing CREB at the time of training became critical components of the engram, we examined memory expression while the activity of these neurons was silenced. Chemogenetically (hM4Di, an inhibitory DREADD receptor) or optogenetically (iC++, a light-activated chloride channel) silencing the small number of CREB-overexpressing DG neurons attenuated memory expression, whereas silencing a similar number of random neurons not overexpressing CREB at the time of training did not. As post-encoding reactivation of the activity patterns present during initial experience is thought to be important in memory consolidation, we investigated whether post-training silencing of neurons allocated to an engram disrupted subsequent memory expression. We found that silencing neurons 5 min (but not 24 h) following training disrupted memory expression. Together these results indicate that the rules of neuronal allocation to an engram originally described in the lateral amygdala are followed in different brain regions including DG, and moreover, that disrupting the post-training activity pattern of these neurons prevents memory consolidation.

The ability to link events that are separated in time is important for extracting meaning from experiences and guiding behavior in the future. This ability likely requires the brain to continue representing events even after they have passed, a process that may involve the prefrontal cortex and takes the form of sustained, event-specific neuron activity. Here, we show that experimentally increasing the activity of excitatory neurons in the medial prefrontal cortex (mPFC) enables rats to associate two stimuli separated by a 750-ms long temporal gap. Learning is accompanied by ramping increases in prefrontal theta and beta rhythms during the interval between stimuli. This ramping activity predicts memory-related behavioral responses on a trial-by-trial basis but is not correlated with the same muscular activity during non-memory conditions. Thus, the enhancement of prefrontal neuron excitability extends the time course of evoked prefrontal network activation and facilitates the formation of associations of temporally disparate, but correlated, events., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)

The medial prefrontal cortex is thought to be important for guiding behavior according to an animal's expectations. Efforts to decode the region have focused not only on the question of what information it computes, but also how distinct circuit components become engaged during behavior. We find that the activity of regular-firing, putative projection neurons contains rich information about behavioral context and firing fields cluster around reward sites, while activity among putative inhibitory and fast-spiking neurons is most associated with movement and accompanying sensory stimulation. These dissociations were observed even between adjacent neurons with apparently reciprocal, inhibitory-excitatory connections. A smaller population of projection neurons with burst-firing patterns did not show clustered firing fields around rewards; these neurons, although heterogeneous, were generally less selective for behavioral context than regular-firing cells. The data suggest a network that tracks an animal's behavioral situation while, at the same time, regulating excitation levels to emphasize high valued positions. In this scenario, the function of fast-spiking inhibitory neurons is to constrain network output relative to incoming sensory flow. This scheme could serve as a bridge between abstract sensorimotor information and single-dimensional codes for value, providing a neural framework to generate expectations from behavioral state., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

What constitutes a "mechanism" of behavior? In this tribute to Jerry Hogan we examine how questions of behavioral mechanism can be reframed as causes and consequences of neural circuit activity. Drawing from our work on the hippocampus and the medial prefrontal cortex we discuss the inherent difficulties of characterizing the behavioral functions of circuits that are many synapses away from sensory reception and motor/visceral expression. We briefly review the advantages of reframing a region's functions according to its computations, while also distinguishing those computations from the algorithms by which they are achieved. As an example of how these ideas can be applied, we discuss why the hippocampus and medial prefrontal cortex may have overlapping roles in memory expression in spite of being very different circuits. The present analysis draws inspiration from David Marr, whose framework for describing neural systems can be compared with Aristotle's "causes." This article is part of a Special Issue entitled: In Honor of Jerry Hogan., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Deep brain stimulation (DBS) of the subgenual cingulate gyrus (SCG) has been used to treat patients with treatment-resistant depression. As in humans, DBS applied to the ventromedial prefrontal cortex of rats induces antidepressant-like responses. Physiological interactions between structures that play a role in depression and antidepressant treatment are still unknown. The present study examined the effect of DBS on inter-region communication by measuring the coherence of local field potentials in the rat infralimbic cortex (IL; homologue of the SCG) and one of its major afferents, the ventral hippocampus (VH). Rats received daily IL DBS treatment (100 μA, 90 μs, 130 Hz; 8h/day). Recordings were conducted in unrestrained, behaving animals on the day before treatment, after 1 and 10 days of treatment, and 10 days stimulation offset. VH-IL coherence in the 2-4 Hz range was reduced in DBS-treated animals compared with shams after 10 days, but not after only 1 day of treatment. No effect of DBS was observed in the 6-10 Hz (theta) range, where coherence was generally high and could be further evoked with a loud auditory stimulus. Finally, coherence was not affected by fluoxetine (10mg/kg), suggesting that the effects of DBS were not likely mediated by increased serotonin levels. While these data support the hypothesis that DBS disrupts communication between regions important for expectation-based control of emotion, they also suggest that lasting physiological effects require many days of treatment and, furthermore, may be specific to lower-frequency patterns, the nature and scope of which await further investigation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Daily experiences are represented by networks of neurons distributed across the neocortex, bound together for rapid storage and later retrieval by the hippocampus. While the hippocampus is necessary for retrieving recent episode-based memory associations, over time, consolidation processes take place that enable many of these associations to be expressed independent of the hippocampus. It is generally thought that mechanisms of consolidation involve synaptic weight changes between cortical regions; or, in other words, the formation of "horizontal" cortico-cortical connections. Here, we review anatomical, behavioral, and physiological data which suggest that the connections in and between the entorhinal and cingulate cortices may be uniquely important for the long-term storage of memories that initially depend on the hippocampus. We propose that current theories of consolidation that divide memory into dual systems of hippocampus and neocortex might be improved by introducing a third, middle layer of entorhinal and cingulate allocortex, the synaptic weights within which are necessary and potentially sufficient for maintaining initially hippocampus-dependent associations over long time periods. This hypothesis makes a number of still untested predictions, and future experiments designed to address these will help to fill gaps in the current understanding of the cortical structure of consolidated memory., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Previous work suggests that activation patterns of neurons in superficial layers of the neocortex are more sensitive to spatial context than activation patterns in deep cortical layers. A possible source of this laminar difference is the distribution of contextual information to the superficial cortical layers carried by hippocampal efferents that travel through the entorhinal cortex and subiculum. To evaluate the role that the hippocampus plays in determining context sensitivity in superficial cortical layers, behavior-induced expression of the immediate early gene Arc was examined in hippocampus-lesioned and control rats after exposing them to 2 distinct contexts. Contrary to expectations, hippocampal lesions had no observable effect on Arc expression in any neocortical layer relative to controls. Furthermore, another group of intact animals was exposed to the same environment twice, to determine the reliability of Arc-expression patterns across identical contextual and behavioral episodes. Although this condition included no difference in external input between 2 epochs, the significant layer differences in Arc expression still remained. Thus, laminar differences in activation or plasticity patterns are not likely to arise from hippocampal sources or differences in external inputs, but are more likely to be an intrinsic property of the neocortex.

A decrease in the ratio of 18O to 16O (delta18O) of sedimentary carbonate from the Bolivian Altiplano has been interpreted to indicate rapid surface uplift of the late Miocene Andean plateau (AP). Here we report on paleoclimate simulations of Andean surface uplift with an atmospheric general circulation model (GCM) that tracks oxygen isotopes in vapor. The GCM predicts changes in atmospheric circulation and rainfall that influence AP isotopic source and amount effects. On eastern AP slopes, summer convective precipitation increases by up to 6 millimeters per day (>500%) for plateau elevations that are greater than about 2000 meters. High precipitation rates enhance the isotope amount effect, leading to a decrease in precipitation delta18O at high elevations and an increase in delta18O lapse rate. Our results indicate that late Miocene delta18O depletion reflects initiation and intensification of convective rainfall.

Studies demonstrating recognition deficits with aging often use tasks in which subjects have an incentive to correctly encode or retrieve the experimental stimuli. In contrast to these tasks, which may engage strategic encoding and retrieval processes, the visual paired comparison (VPC) task measures spontaneous eye movements made toward a novel as compared with familiar stimulus. In the present study, seven rhesus macaques aged 6 to 30 years exhibited a dramatic age-dependent decline in preference for a novel image compared with one presented seconds earlier. The age effect could not be accounted for by memory deficits alone, because it was present even when familiarization preceded test by 1 second. It also could not be explained by an encoding deficit, because the effect persisted with increased familiarity of the sample stimulus. Reduced novelty preference did correlate with eye movement variables, including reaction time distributions and saccade frequency. At long delay intervals (24 or 48 hours) aging was paradoxically associated with increased novelty preference. Several explanations for the age effect are considered, including the possible role of dopamine.

Active behavior, such as exploring a novel environment, induces the expression of the immediate-early gene Arc (activity-regulated cytoskeletal associated protein, or Arg 3.1) in many brain regions, including the hippocampus, neocortex, and striatum. Arc messenger ribonucleic acid and protein are localized in activated dendrites, and Arc protein is required for the maintenance of long-term potentiation and memory consolidation. Although previous evidence suggests that Arc is expressed in neurons, there is no direct demonstration that only neurons can express Arc. Furthermore, there is no characterization of the main neuronal types that express Arc. The data reported here show that behavior- or seizure-induced Arc expression in the hippocampus, primary somatosensory cortex, and dorsal striatum of rats colocalizes only with neuronal (NeuN-positive) and not with glial (GFAP-positive) cells. Furthermore, Arc was found exclusively in non-GABAergic alpha-CaMKII-positive hippocampal and neocortical neurons of rats that had explored a novel environment. Some GAD65/67-positive neurons in these regions were observed to express Arc, but only after a very strong stimulus (electroconvulsive seizure). In the dorsal striatum, spatial exploration induced Arc only in GABAergic and alpha-CaMKII-positive neurons. Combined, these results show that although a very strong stimulus (seizure) can induce Arc in a variety of neurons, behavior induces Arc in the CaMKII-positive principal neurons of the hippocampus, neocortex, and dorsal striatum. These results, coupled with recent in vitro findings of interactions between Arc and CaMKII, are consistent with the hypothesis that Arc and CaMKII act as plasticity partners to promote functional and/or structural synaptic modifications that accompany learning.