Dopamine release and dopamine-related gene expression in the amygdala are modulated by the gastrin-releasing peptide in opposite directions during stress-enhanced fear learning and extinction.

Fear extinction leads to a decrease of originally acquired fear responses after the threat is no longer present. Fear extinction is adaptive and critical for organism's survival, but deficits in extinction may lead to exaggerated fear in animals or post-traumatic stress disorder (PTSD) in humans. Dopamine has recently emerged as essential for fear extinction and PTSD, however the neural circuits serving this dopamine function are only beginning to be investigated, and the dopamine intracellular signaling pathways are unknown.

Distribution, cellular localization, and colocalization of several peptide neurotransmitters in the central nervous system of .

Neuropeptides are widely used as neurotransmitters in vertebrates and invertebrates. In vertebrates, a detailed understanding of their functions as transmitters has been hampered by the complexity of the nervous system. The marine mollusk , with a simpler nervous system and many large, identified neurons, presents several advantages for addressing this question and has been used to examine the roles of tens of peptides in behavior.

CPEB3 low-complexity motif regulates local protein synthesis via protein-protein interactions in neuronal ribonucleoprotein granules.

Biomolecular condensates, membraneless organelles found throughout the cell, play critical roles in many aspects of cellular function. Ribonucleoprotein granules (RNPs) are a type of biomolecular condensate necessary for local protein synthesis and are involved in synaptic plasticity and long-term memory. Most of the proteins in RNPs possess low-complexity motifs (LCM), allowing for increased promiscuity of protein-protein interactions.

Synaptoproteomic Analysis of the Prefrontal Cortex Reveals Spatio-Temporal Changes in SYNGAP1 Following Cannabinoid Exposure in Rat Adolescence.

The regular use of cannabis during adolescence has been associated with a number of negative life outcomes, including psychopathology and cognitive impairments. However, the exact molecular mechanisms that underlie these outcomes are just beginning to be understood. Moreover, very little is known about the spatio-temporal molecular changes that occur following cannabinoid exposure in adolescence.

A missense mutation in causes hippocampal learning deficits in mice.

Although a wide variety of genetic tools has been developed to study learning and memory, the molecular basis of memory encoding remains incompletely understood. Here, we undertook an unbiased approach to identify novel genes critical for memory encoding. From a large-scale, in vivo mutagenesis screen using contextual fear conditioning, we isolated in mice a mutant, named , with spatial learning deficits.

The evolution of synaptic and cognitive capacity: Insights from the nervous system transcriptome of .

The gastropod mollusk is an important model for cellular and molecular neurobiological studies, particularly for investigations of molecular mechanisms of learning and memory. We developed an optimized assembly pipeline to generate an improved nervous system transcriptome. This improved transcriptome enabled us to explore the evolution of cognitive capacity at the molecular level.

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

The hippocampus is essential for different forms of declarative memory, including social memory, the ability to recognize and remember a conspecific. Although recent studies identify the importance of the dorsal CA2 region of the hippocampus in social memory storage, little is known about its sources of social information. Because CA2, like other hippocampal regions, receives its major source of spatial and non-spatial information from the medial and lateral subdivisions of entorhinal cortex (MEC and LEC), respectively, we investigated the importance of these inputs for social memory.

A fast, aqueous, reversible three-day tissue clearing method for adult and embryonic mouse brain and whole body.

Optical clearing methods serve as powerful tools to study intact organs and neuronal circuits. We developed an aqueous clearing protocol, Fast 3D Clear, that relies on tetrahydrofuran for tissue delipidation and iohexol for clearing, such that tissues can be imaged under immersion oil in light-sheet imaging systems. Fast 3D Clear requires 3 days to achieve high transparency of adult and embryonic mouse tissues while maintaining their anatomical integrity and preserving a vast array of transgenic and viral/dye fluorophores.

Deep brain stimulation of the nucleus accumbens shell attenuates cocaine withdrawal but increases cocaine self-administration, cocaine-induced locomotor activity, and GluR1/GluA1 in the central nucleus of the amygdala in male cocaine-dependent rats.

Background: Cocaine addiction is a major public health problem. Despite decades of intense research, no effective treatments are available. Both preclinical and clinical studies strongly suggest that deep brain stimulation of the nucleus accumbens (NAcc) is a viable target for the treatment of cocaine use disorder (CUD).

3D neuronal mitochondrial morphology in axons, dendrites, and somata of the aging mouse hippocampus.

The brain's ability to process complex information relies on the constant supply of energy through aerobic respiration by mitochondria. Neurons contain three anatomically distinct compartments-the soma, dendrites, and projecting axons-which have different energetic and biochemical requirements, as well as different mitochondrial morphologies in cultured systems. In this study, we apply quantitative three-dimensional electron microscopy to map mitochondrial network morphology and complexity in the mouse brain.

Possible novel features of synaptic regulation during long-term facilitation in .

Most studies of molecular mechanisms of synaptic plasticity have focused on the sequence of changes either at individual synapses or in the cell nucleus. However, studies of long-term facilitation at sensory neuron-motor neuron synapses in isolated cell culture suggest two additional features of facilitation. First, that there is also regulation of the number of synaptic contacts between two neurons, which may occur at the level of cell pair-specific branch points in the neuronal arbor.

Enkephalin release from VIP interneurons in the hippocampal CA2/3a region mediates heterosynaptic plasticity and social memory.

The hippocampus contains a diverse array of inhibitory interneurons that gate information flow through local cortico-hippocampal circuits to regulate memory storage. Although most studies of interneurons have focused on their role in fast synaptic inhibition mediated by GABA release, different classes of interneurons express unique sets of neuropeptides, many of which have been shown to exert powerful effects on neuronal function and memory when applied pharmacologically. However, relatively little is known about whether and how release of endogenous neuropeptides from inhibitory cells contributes to their behavioral role in regulating memory formation.

Loss of retinoid X receptor gamma subunit impairs group 1 mGluR mediated electrophysiological responses and group 1 mGluR dependent behaviors.

Retinoid X receptors are members of the nuclear receptor family that regulate gene expression in response to retinoic acid and related ligands. Group 1 metabotropic glutamate receptors are G-protein coupled transmembrane receptors that activate intracellular signaling cascades in response to the neurotransmitter, glutamate. These two classes of molecules have been studied independently and found to play important roles in regulating neuronal physiology with potential clinical implications for disorders such as depression, schizophrenia, Parkinson's and Alzheimer's disease.

An objective evaluation of the beholder's response to abstract and figurative art based on construal level theory.

Does abstract art evoke a different cognitive state than figurative art? To address this question empirically, we bridged art theory and cognitive research and designed an experiment leveraging construal level theory (CLT). CLT is based on experimental data showing that psychologically distant events (i.e.

Cytoplasmic Polyadenylation Element Binding Proteins CPEB1 and CPEB3 Regulate the Translation of FosB and Are Required for Maintaining Addiction-Like Behaviors Induced by Cocaine.

A recurrent and devastating feature of addiction to a drug of abuse is its persistence, which is mediated by maladaptive long-term memories of the highly pleasurable experience initially associated with the consumption of the drug. We have recently found that members of the CPEB family of proteins (Cytoplasmic Polyadenylation Element-Binding Proteins) are involved in the maintenance of spatial memory. However, their possible role in the maintenance of memories that sustain addictive behavior has yet to be explored.

Cannabinoid exposure in rat adolescence reprograms the initial behavioral, molecular, and epigenetic response to cocaine.

The initial response to an addictive substance can facilitate repeated use: That is, individuals experiencing more positive effects are more likely to use that drug again. Increasing evidence suggests that psychoactive cannabinoid use in adolescence enhances the behavioral effects of cocaine. However, despite the behavioral data, there is no neurobiological evidence demonstrating that cannabinoids can also alter the brain's initial molecular and epigenetic response to cocaine.

Comparison of the ionic currents modulated during activity-dependent and normal presynaptic facilitation.

One of the major questions in psychology is whether associative and nonassociative learning are fundamentally different or whether they involve similar processes and mechanisms. We have addressed this question by comparing mechanisms of a nonassociative form of learning, sensitization, and an associative form of learning, classical conditioning of the siphon-withdrawal reflex of hermaphroditic In an analog of differential conditioning, action potentials in one siphon sensory neuron (SN) were paired with shock to the pedal nerves, producing activity-dependent presynaptic facilitation, and action potentials in another SN were unpaired with the shock as a control. The difference between paired and unpaired training is a measure of associative plasticity.

Single-nucleotide polymorphism in the human TIA1 gene interacts with stressful life events to predict the development of pathological anxiety symptoms in a Swedish population.

Background: The TIA1 gene encodes a prion-related RNA-binding protein that regulates stress-dependent synaptic plasticity and fear memory in mice. It is unknown whether genetic variation in human TIA1 is associated with differences in stress- and fear-related behavior in people.

Methods: A longitudinal, population-based survey was conducted in Sweden to collect information on demographics, socioeconomic status, exposure to stressful life events and psychiatric symptoms.

Serotonin Induces Structural Plasticity of Both Extrinsic Modulating and Intrinsic Mediating Circuits In Vitro in Aplysia Californica.

Long-term sensitization of the gill withdrawal reflex in Aplysia requires heterosynaptic, modulatory input that is mediated in part by the growth of new synaptic connections between sensory neurons and their follower cells (intrinsic mediating circuit). Whether modulatory interneurons (the extrinsic modulatory circuit) also display learning-related structural synaptic plasticity remains unknown. To test this idea, we added a bona fide serotonergic modulatory neuron, the metacerebral cell (MCC), to sensory-motor neuron co-cultures and examined the modulating presynaptic varicosities of MCCs before and after repeated pulses of serotonin (5-HT) that induced long-term facilitation (LTF).

Ubiquitination and SUMOylation of Amyloid and Amyloid-like Proteins in Health and Disease.

Post-translational modifications (PTMs) play important roles in altering the structure and function of proteins. In this article, we focus on ubiquitination and SUMOylation of amyloidogenic proteins. We discuss the functional contributions of PTMs on proteins involved in amyloid-related diseases as well as the aberrant PTM signatures of the disease agents.

CPEB3 inhibits translation of mRNA targets by localizing them to P bodies.

Protein synthesis is crucial for the maintenance of long-term memory-related synaptic plasticity. The cytoplasmic polyadenylation element-binding protein 3 (CPEB3) regulates the translation of several mRNAs important for long-term synaptic plasticity in the hippocampus. In previous studies, we found that the oligomerization and activity of CPEB3 are controlled by small ubiquitin-like modifier (SUMO)ylation.

Sex Differences in Remote Contextual Fear Generalization in Mice.

The generalization of fear is adaptive in that it allows an animal to respond appropriately to novel threats that are not identical to previous experiences. In contrast, the overgeneralization of fear is maladaptive and is a hallmark of post-traumatic stress disorder (PTSD), a psychiatric illness that is characterized by chronic symptomatology and a higher incidence in women compared to men. Therefore, understanding the neural basis of fear generalization at remote time-points in female animals is of particular translational relevance.