Hippocampal oscillations arise from coordinated activity among distinct populations of neurons and are associated with cognitive functions. Much progress has been made toward identifying the contribution specific neuronal in hippocampal oscillations, but less is known about role area CA2, which thought to support social memory. Furthermore, little evidence on CA2 yielded conflicting conclusions. Therefore, we sought identify using a controlled experimental system. We used excitatory...

Mineralocorticoid receptors (MRs) in the brain play a role learning and memory, neuronal differentiation, regulation of stress response. Within hippocampus, highest expression MRs is area CA2. CA2 pyramidal neurons have distinct molecular makeup resulting plasticity-resistant phenotype, distinguishing them from CA1 CA3. Thus, we asked whether regulate neuron properties CA2-related behaviors. Using three conditional knockout methods at different stages development, found striking decrease...

Perineuronal nets (PNNs), a specialized form of extracellular matrix, are abnormal in the brains people with Rett syndrome (RTT). We previously reported that PNNs function to restrict synaptic plasticity hippocampal area CA2, which is unusually resistant long-term potentiation (LTP) and has been linked social learning mice. Here we report appear elevated CA2 hippocampus an individual RTT develop precociously remain mouse model (Mecp2-null). Further, provide evidence LTP could be induced at...

Pyramidal neurons in hippocampal area CA2 are distinct from neighboring CA1 that they resist synaptic long-term potentiation (LTP) at CA3 Schaffer collateral synapses. Regulator of G protein signaling 14 (RGS14) is a complex scaffolding enriched dendritic spines naturally blocks plasticity and hippocampus-dependent learning, but the cellular mechanisms by which RGS14 gates LTP largely unexplored. A previous study has attributed lack to higher rates calcium (Ca2+) buffering extrusion spines....

The noradrenergic locus coeruleus (LC) is among the earliest sites of tau and α-synuclein pathology in Alzheimer's disease (AD) Parkinson's (PD), respectively. onset these pathologies coincides with loss fibers LC target regions emergence prodromal symptoms including sleep disturbances anxiety. Paradoxically, are indicative a hyperactivity phenotype, rather than predicted norepinephrine (NE) transmission following damage, suggesting engagement complex compensatory mechanisms. Because current...

Activity of hippocampal pyramidal cells is critical for certain forms learning and memory, work from our lab others has shown that CA2 neuronal activity required social cognition behavior. Silencing neurons in mice impairs lacking Regulator G-Protein Signaling 14 (RGS14), a protein highly enriched neurons, learn faster than wild types the Morris water maze spatial memory test. Although enhanced abilities RGS14 KO suggest role at least one hippocampus-dependent behavior, fear conditioning,...

Abstract Pyramidal cells in hippocampal area CA2 have synaptic properties that are distinct from the other CA subregions. Notably, this includes a lack of typical long‐term potentiation stratum radiatum synapses. neurons express high levels several known and potential regulators metabotropic glutamate receptor (mGluR)‐dependent signaling including Striatal‐Enriched Tyrosine Phosphatase (STEP) Regulator G‐protein Signaling (RGS) proteins, yet functions these proteins regulating...

Regulator of G Protein Signaling 14 (RGS14) is a complex scaffolding protein that integrates and MAPK signaling pathways. In the adult mouse brain, RGS14 predominantly expressed in hippocampal CA2 neurons where it naturally inhibits synaptic plasticity hippocampus-dependent learning memory. However, proteins natively engages to regulate are unknown. Here, we show exists high-molecular-weight brain. To identify neuronal interacting partners, endogenous immunoprecipitated from brain was...

In rodents, exposure to predator odors such as cat urine acts a severe stressor that engages innate defensive behaviors critical for survival in the wild. The neurotransmitters norepinephrine (NE) and dopamine (DA) modulate anxiety odor responses, we have shown previously β-hydroxylase knockout (Dbh −/−), which reduces NE increases DA mouse noradrenergic neurons, disrupts response mild stressors novelty. We examined consequences of Dbh −/−) on responses (bobcat urine) compared them...

RGS14 is a complex multifunctional scaffolding protein that highly enriched within pyramidal cells (PCs) of hippocampal area CA2. In these neurons, suppresses glutamate-induced calcium influx and related G ERK signaling in dendritic spines to restrain postsynaptic plasticity. Previous findings show that, unlike PCs areas CA1 CA3, CA2 are resistant number neurological insults, including degeneration caused by temporal lobe epilepsy (TLE). While protective against peripheral injury, similar...

The human genome contains vast genetic diversity as naturally occurring coding variants, yet the impact of these variants on protein function and physiology is poorly understood. RGS14 a multifunctional signaling that suppresses synaptic plasticity in dendritic spines hippocampal neurons. also nucleocytoplasmic shuttling protein, suggesting balanced nuclear import/export spine localization are essential for functions. We identified L505R (LR) R507Q (RQ) located within export sequence (NES)...

RGS14 is a complex multifunctional scaffolding protein that highly enriched within pyramidal cells (PCs) of hippocampal area CA2. There, suppresses glutamate-induced calcium influx and related G ERK signaling in dendritic spines to restrain postsynaptic plasticity. Previous findings show that, unlike PCs areas CA1 CA3, CA2 are resistant number neurological insults, including degeneration caused by temporal lobe epilepsy (TLE). While protective against peripheral injury, similar roles for...

Abstract The noradrenergic locus coeruleus (LC) is among the earliest sites of tau and alpha-synuclein pathology in Alzheimer’s disease (AD) Parkinson’s (PD), respectively. onset these pathologies coincides with loss fibers LC target regions emergence prodromal symptoms including sleep disturbances anxiety. Paradoxically, are indicative a hyperactivity phenotype, rather than predicted norepinephrine (NE) transmission following damage, suggesting engagement complex compensatory mechanisms....

Abstract Hippocampal oscillations arise from coordinated activity among distinct populations of neurons and are associated with cognitive functions behaviors. Although much progress has been made toward identifying the relative contribution specific neuronal in hippocampal oscillations, far less is known about role area CA2, which thought to support social aspects episodic memory. Furthermore, little existing evidence on CA2 led conflicting conclusions. Therefore, we sought identify...

ABSTRACT Accumulating evidence indicates that disruption of galanin signaling is associated with neuropsychiatric disease, but the precise functions this neuropeptide remain largely unresolved due to lack tools for experimentally disrupting its transmission in a cell type-specific manner. To examine function noradrenergic system, we generated and crossed two novel knock-in mouse lines create animals lacking specifically neurons ( Gal cKO-Dbh ). We observed reduced levels peptide pons,...

Abstract Rationale Obsessive-compulsive disorder (OCD) is characterized by repetitive behaviors exacerbated stress. Many OCD patients do not respond to available pharmacotherapies, but neurosurgical ablation of the anterior cingulate cortex (ACC) can provide symptomatic relief. Although ACC receives noradrenergic innervation and expresses adrenergic receptors (ARs), involvement norepinephrine (NE) in has been investigated. Objective To determine effects genetic or pharmacological disruption...

Abstract Pyramidal neurons in hippocampal area CA2 are distinct from neighboring CA1 that they resist synaptic long-term potentiation (LTP) at CA3 Schaffer Collateral synapses. Regulator of G Protein Signaling 14 (RGS14) is a complex scaffolding protein enriched dendritic spines naturally blocks plasticity and hippocampus-dependent learning, but the cellular mechanisms by which RGS14 gates LTP largely unexplored. A previous study has attributed lack to higher rates calcium (Ca 2+ ) buffering...

Abstract The human genome contains vast genetic diversity in the form of naturally occurring coding variants, yet impact these variants on protein function and physiology is poorly understood. RGS14 a multifunctional signaling that suppresses synaptic plasticity dendritic spines hippocampal neurons. also nucleocytoplasmic shuttling protein, suggesting balanced nuclear import/export spine localization are essential for functions. We identified L505R (LR) R507Q (RQ) located within export...

ABSTRACT Background Both the noradrenergic and galaninergic systems have been implicated in stress-related neuropsychiatric disorders, these two neuromodulators are co-released from stress-responsive locus coeruleus (LC); however, individual contributions of LC-derived norepinephrine (NE) galanin to behavioral stress responses unclear. Here we aimed disentangle functional roles NE stress-induced behavior. Methods We used foot shock, optogenetics, pharmacology wild-type (WT) mice lacking...