Biology subjects

de Solis, C. A.

Publications and source records attributed to de Solis, C. A..

5 recordsLinked to original sources

bioRxiv2022

Corticotropin-releasing hormone signaling from prefrontal cortex to lateral septum supports social novelty preference

Social preference, the decision to interact with one member of the same species over another, is a key feature of optimizing social interactions. In rodents, social preference relies on both extrinsic factors, such as sex, strain and kinship, and intrinsic ones, such as the memory of previous encounters, which favors interactions with novel compared to familiar animals (social novelty preference). At present, it is unclear which neuronal circuits guide social preferences and whether such circuits promote social interactions with the preferred individuals or suppress interactions with the non-preferred ones. Although both the infra-limbic area of the pre-frontal cortex (ILA) and the lateral septum (LS) have been shown to support social novelty preference, the neuronal circuits and molecular mechanisms by which these brain regions interact to regulate social interactions are unknown. Here, we identify a population of inhibitory neurons in ILA that express the neuropeptide corticotropin releasing hormone (CRH) and project to the rostro-dorsal region of LS (rdLS). Release of CRH from ILA in rdLS during interactions with familiar mice disinhibits rdLS neurons, thereby suppressing interactions with familiar mice and contributing to social novelty preference. We further demonstrate how the maturation of CRH expression during the first two post-natal weeks enables the developmental shift from a preference for littermates in juveniles to a preference for novel mice in adults.

neuroscience↗

bioRxiv2021

A multisensory circuit for gating intense aversive experiences

The ventral hippocampus (vHPC) is critical for both learned and innate fear, but how discrete projections control different types of fear is poorly understood. Here, we report a novel excitatory circuit from a subpopulation of the ventral hippocampus CA1 subfield (vCA1) to the inhibitory peri-paraventricular nucleus of the hypothalamus (pPVN) which then routes to the periaqueductal grey (PAG). We find that vCA1[->]pPVN projections modulate both learned and innate fear. Fiber photometric calcium recordings reveal that activity in vCA1[->]pPVN projections increases during the first moments of exposure to an unconditioned threat. Chemogenetic or optogenetic silencing of vCA1[->]pPVN cell bodies or vCA1[->]pPVN axon terminals in the pPVN enhances the initial magnitude of both active and passive unconditioned defensive responses, irrespective of the sensory modalities engaged by a particular innate threat. Moreover, silencing produces a dramatic impact on learned fear without affecting milder anxiety-like behaviors. We also show that vCA1[->]pPVN projections monosynaptically route to the PAG, a key brain region that orchestrates the fear response. Surprisingly, optogenetic silencing of vCA1 terminals in the pPVN titrates the level of c-Fos neural activity in the PAG differently for learned versus innate threats. Together, our results show how a novel vCA1[->]pPVN circuit modulates neuronal activity in the PAG to regulate both learned and innate fear. These findings have implications for how initial trauma processing may influence maladaptive defensive behaviors across fear and trauma-related disorders. One Sentence SummaryA multisensory gate for high intensity aversive experiences.

neuroscience↗

bioRxiv2021

A direct lateral entorhinal cortex to hippocampal CA2 circuit conveys social information required for social memory

The storage of information by the hippocampus in long-term memory is thought to involve two distinct but related processes. First, the hippocampus determines whether a given stimulus is novel or familiar; next, the hippocampus stores the novel information in long-term memory. To date, the neural circuits that detect novelty and their relation to the circuits that store information of a specific memory are poorly understood. Here we address this question by examining the circuits by which the CA2 region of the hippocampus, which is essential for social memory, both detects social novelty and stores social memory. CA2, like the more thoroughly studied CA1 region, receives its major excitatory input from the entorhinal cortex through both a direct monosynaptic and indirect trisynaptic pathway. We find that the direct inputs to CA2 from the lateral entorhinal cortex, but not the indirect trisynaptic inputs, provide social information that is required for social memory. However, these direct inputs fail to discriminate a novel from a familiar animal. Thus, social novelty and social identity signals are likely conveyed through separate pathways, with the entorhinal cortex providing specific multisensory information about an animals identity and novelty detection requiring a local computation within CA2.

neuroscience↗

bioRxiv2020

The low complexity motif of cytoplasmic polyadenylation element binding protein 3 (CPEB3) is critical for the trafficking of its targets in neurons

Biomolecular condensates, membraneless organelles found throughout the cell, play critical roles in many aspects of cellular function. Ribonucleoprotein granules (RNPs), a type of biomolecular condensate found in neurons that are necessary for local protein synthesis and are involved in long-term potentiation (LTP). Several RNA-binding proteins present in RNPs are necessary for the synaptic plasticity involved in LTP and long-term memory. Most of these proteins possess low complexity motifs, allowing for increased promiscuity. We explore the role the low complexity motif plays for RNA binding protein cytoplasmic polyadenylation element binding protein 3 (CPEB3), a protein necessary for long-term memory persistence. We found that RNA binding and SUMOylation are necessary for CPEB3 localization to the P body, thereby having functional implications on translation. Here, we investigate the role of the low complexity motif of CPEB3 and find that it is necessary for P body localization and downstream targeting for local protein synthesis.

neuroscience↗

bioRxiv2019

Increasing Synaptic GluN2B levels within the Basal and Lateral Amygdala Enables the Modification of Strong Reconsolidation Resistant Fear Memories

Reconsolidation disruption has been proposed as a method to attenuate pathological memories in disorders such as PTSD. However, studies from our group and others indicate that strong memories are resistant to becoming destabilized following reactivation, rendering them impervious to agents that disrupt the re-stabilization phase of reconsolidation. Thus, therapies designed to attenuate maladaptive memories by disrupting reconsolidation updating have not been adequately developed. We previously determined that animals possessing strong auditory fear memories, compared to animals with weaker fear memories, are associated with an enduring increase in the synaptic GluN2A/GluN2B ratio in neurons of the mouse basal and lateral amygdala (BLA). In this study, we determined whether increasing GluN2B levels within BLA excitatory neuronal synapses is sufficient to enable modification of strong fear memories via reconsolidation. To accomplish this, we utilized a combinatorial genetic strategy to express GluN2B or GluN2B(E1479Q) in excitatory neurons of the mouse BLA before or after fear memory consolidation. GluN2B(E1479Q) contains a point mutation that increases synaptic expression of the subunit by interfering with phosphorylation-driven endocytosis. At the time of memory retrieval, increasing synaptic GluN2B levels by expression of GluN2B(E1479Q), but not GluN2B(WT), enhanced the induction of reconsolidation rendering the strong fear memory modifiable. GluN2B(WT) or GluN2B(E1479Q) expression did not influence fear memory maintenance or extinction. Fear memory consolidation, however, was enhanced when GluN2B(E1479Q) was expressed in the BLA at the time of training. These findings indicate that enhancing GluN2B synaptic trafficking may provide a novel therapeutic strategy to enhance modification of pathological memories.

neuroscience↗