Deletion of endocannabinoid synthesizing enzyme DAGLα from cerebellar Purkinje cells decreases social preference and elevates anxiety.

The endocannabinoid (eCB) signaling system is robustly expressed in the cerebellum starting from the embryonic developmental stages to adulthood. There it plays a key role in regulating cerebellar synaptic plasticity and excitability, suggesting that impaired eCB signaling will lead to deficits in cerebellar adjustments of ongoing behaviors and cerebellar learning. Indeed, human mutations in are associated with neurodevelopmental disorders.

Synaptic Plasticity in the Injured Brain Depends on the Temporal Pattern of Stimulation.

Neurostimulation protocols are increasingly used as therapeutic interventions, including for brain injury. In addition to the direct activation of neurons, these stimulation protocols are also likely to have downstream effects on those neurons' synaptic outputs. It is well known that alterations in the strength of synaptic connections (long-term potentiation, LTP; long-term depression, LTD) are sensitive to the frequency of stimulation used for induction; however, little is known about the contribution of the temporal pattern of stimulation to the downstream synaptic plasticity that may be induced by neurostimulation in the injured brain.

ADGRL1 is a glucose receptor involved in mediating energy and glucose homeostasis.

Aims/hypothesis: The brain is a major consumer of glucose as an energy source and regulates systemic glucose as well as energy balance. Although glucose transporters such as GLUT2 and sodium-glucose cotransporter 2 (SGLT2) are known to regulate glucose homeostasis and metabolism, the identity of a receptor that binds glucose to activate glucose signalling pathways in the brain is unknown. In this study, we aimed to discover a glucose receptor in the mouse hypothalamus.

Activity of cat premotor cortex neurons during visually guided stepping.

Visual control of steps is critical in everyday life. Several motor centers are implicated in visual control of steps on a complex surface, however, participation of a large cortical motor area, the premotor cortex, in visual guidance of steps during overground locomotion has not been examined. Here, we analyzed the activity of neurons in feline premotor cortex areas 6aα and 6aγ as cats walked on the flat surface where visual guidance of steps is not needed and stepped on crosspieces of a horizontally placed ladder or over barriers where visual control of steps is required.

TREM2 splice isoforms generate soluble TREM2 species that disrupt long-term potentiation.

Background: TREM2 is a transmembrane receptor expressed by myeloid cells and acts to regulate their immune response. TREM2 governs the response of microglia to amyloid and tau pathologies in the Alzheimer's disease (AD) brain. TREM2 is also present in a soluble form (sTREM2), and its CSF levels fluctuate as a function of AD progression.

Bassoon contributes to tau-seed propagation and neurotoxicity.

Tau aggregation is a defining histopathological feature of Alzheimer's disease and other tauopathies. However, the cellular mechanisms involved in tau propagation remain unclear. Here, we performed an unbiased quantitative proteomic study to identify proteins that specifically interact with this tau seed.

The role of anterior insular cortex inputs to dorsolateral striatum in binge alcohol drinking.

How does binge drinking alcohol change synaptic function, and do these changes maintain binge consumption? The anterior insular cortex (AIC) and dorsolateral striatum (DLS) are brain regions implicated in alcohol use disorder. In male, but not female mice, we found that binge drinking alcohol produced glutamatergic synaptic adaptations selective to AIC inputs within the DLS. Photoexciting AIC→DLS circuitry in male mice during binge drinking decreased alcohol, but not water consumption and altered alcohol drinking mechanics.

Prenatal Opioid Exposure Impairs Endocannabinoid and Glutamate Transmission in the Dorsal Striatum.

The opioid crisis has contributed to a growing population of children exposed to opioids during fetal development; however, many of the long-term effects of opioid exposure on development are unknown. We previously demonstrated that opioids have deleterious effects on endocannabinoid plasticity at glutamate synapses in the dorsal striatum of adolescent rodents, but it is unclear whether prenatal opioid exposure produces similar neuroadaptations. Using a mouse model of prenatal methadone exposure (PME), we performed proteomics, phosphoproteomics, and patch-clamp electrophysiology in the dorsolateral striatum (DLS) and dorsomedial striatum (DMS) to examine synaptic functioning in adolescent PME offspring.

Signals from posterior parietal area 5 to motor cortex during locomotion.

Area 5 of the parietal cortex is part of the "dorsal stream" cortical pathway which processes visual information for action. The signals that area 5 ultimately conveys to motor cortex, the main area providing output to the spinal cord, are unknown. We analyzed area 5 neuronal activity during vision-independent locomotion on a flat surface and vision-dependent locomotion on a horizontal ladder in cats focusing on corticocortical neurons (CCs) projecting to motor cortex from the upper and deeper cortical layers and compared it to that of neighboring unidentified neurons (noIDs).

Trem2 Y38C mutation and loss of Trem2 impairs neuronal synapses in adult mice.

Background: Triggering receptor expressed on myeloid cells 2 (TREM2) is expressed in the brain exclusively on microglia and genetic variants are linked to neurodegenerative diseases including Alzheimer's disease (AD), frontotemporal dementia (FTD) and Nasu Hakola Disease (NHD). The Trem2 variant R47H, confers substantially elevated risk of developing late onset Alzheimer's disease, while NHD-linked Trem2 variants like Y38C, are associated with development of early onset dementia with white matter pathology. However, it is not known how these Trem2 species, predisposes individuals to presenile dementia.

eIF2α-mediated translational control regulates the persistence of cocaine-induced LTP in midbrain dopamine neurons.

Recreational drug use leads to compulsive substance abuse in some individuals. Studies on animal models of drug addiction indicate that persistent long-term potentiation (LTP) of excitatory synaptic transmission onto ventral tegmental area (VTA) dopamine (DA) neurons is a critical component of sustained drug seeking. However, little is known about the mechanism regulating such long-lasting changes in synaptic strength.

Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring.

Maternal obesity during pregnancy has been associated with increased risk of neurodevelopmental disorders, including autism spectrum disorder (ASD), in offspring. Here, we report that maternal high-fat diet (MHFD) induces a shift in microbial ecology that negatively impacts offspring social behavior. Social deficits and gut microbiota dysbiosis in MHFD offspring are prevented by co-housing with offspring of mothers on a regular diet (MRD) and transferable to germ-free mice.

Translational control by eIF2α phosphorylation regulates vulnerability to the synaptic and behavioral effects of cocaine.

Adolescents are especially prone to drug addiction, but the underlying biological basis of their increased vulnerability remains unknown. We reveal that translational control by phosphorylation of the translation initiation factor eIF2α (p-eIF2α) accounts for adolescent hypersensitivity to cocaine. In adolescent (but not adult) mice, a low dose of cocaine reduced p-eIF2α in the ventral tegmental area (VTA), potentiated synaptic inputs to VTA dopaminergic neurons, and induced drug-reinforced behavior.

Translational control of nicotine-evoked synaptic potentiation in mice and neuronal responses in human smokers by eIF2α.

Adolescents are particularly vulnerable to nicotine, the principal addictive component driving tobacco smoking. In a companion study, we found that reduced activity of the translation initiation factor eIF2α underlies the hypersensitivity of adolescent mice to the effects of cocaine. Here we report that nicotine potentiates excitatory synaptic transmission in ventral tegmental area dopaminergic neurons more readily in adolescent mice compared to adults.

Translational control of mGluR-dependent long-term depression and object-place learning by eIF2α.

At hippocampal synapses, activation of group I metabotropic glutamate receptors (mGluRs) induces long-term depression (LTD), which requires new protein synthesis. However, the underlying mechanism remains elusive. Here we describe the translational program that underlies mGluR-LTD and identify the translation factor eIF2α as its master effector.

Initiation of locomotion in lampreys.

The spinal circuitry underlying the generation of basic locomotor synergies has been described in substantial detail in lampreys and the cellular mechanisms have been identified. The initiation of locomotion, on the other hand, relies on supraspinal networks and the cellular mechanisms involved are only beginning to be understood. This review examines some of the findings relative to the neural mechanisms involved in the initiation of locomotion of lampreys.

On the co-occurrence of startles and hippocampal sharp waves in newborn rats.

Hippocampal sharp waves (SPWs) are among the earliest neural population patterns observed in infant mammals. Similarly, startles are among the earliest behavioral events observed. Here we provide evidence indicating that these two events are linked mechanistically soon after birth in freely moving and head-fixed 1 to 4-day-old rats.

Excitatory actions of the ventral midline thalamus (rhomboid/reuniens) on the medial prefrontal cortex in the rat.

The medial prefrontal cortex (mPFC) has been associated with diverse functions including attentional processes, visceromotor activity, decision making, goal directed behavior, and working memory. The present report examined the effects of stimulation of the midline thalamus, concentrating on ventral nuclei of the midline thalamus, on evoked activity at the mPFC. The nucleus reuniens (RE) of the ventral midline thalamus is a major source of projections to the hippocampus and to the mPFC, and has been shown to exert pronounced excitatory effects on the hippocampus.

Theta rhythm of the hippocampus: subcortical control and functional significance.

The theta rhythm is the largest extracellular synchronous signal that can be recorded from the mammalian brain and has been strongly implicated in mnemonic processes of the hippocampus. We describe (a) ascending brain stem-forebrain systems involved in controlling theta and nontheta (desynchronization) states of the hippocampal electroencephalogram; (b) theta rhythmically discharging cells in several structures of Papez's circuit and their possible functional significance, specifically with respect to head direction cells in this same circuit; and (c) the role of nucleus reuniens of the thalamus as a major interface between the medial prefrontal cortex and hippocampus and as a prominent source of afferent limbic information to the hippocampus. We suggest that the hippocampus receives two main types of input: theta rhythm from ascending brain stem- diencephaloseptal systems and information bearing mainly from thalamocortical/cortical systems.

Is partial coherence a viable technique for identifying generators of neural oscillations?

Partial coherence measures the linear relationship between two signals after the influence of a third signal has been removed. Gersch proposed in 1970 that partial coherence could be used to identify sources of driving for multivariate time series. This idea, referred to in this paper as Gersch Causality, has received wide acceptance and has been applied extensively to a variety of fields in the signal processing community.

Quantitative investigation of calcium signals for locomotor pattern generation in the lamprey spinal cord.

Locomotor pattern generation requires the network coordination of spinal ventral horn neurons acting in concert with the oscillatory properties of individual neurons. In the spinal cord, N-methyl-d-aspartate (NMDA) activates neuronal oscillators that are believed to rely on Ca(2+) entry to the cytosol through voltage-operated Ca(2+) channels and synaptically activated NMDA receptors. Ca(2+) signaling in lamprey ventral horn neurons thus plays a determinant role in the regulation of the intrinsic membrane properties and network synaptic interaction generating spinal locomotor neural pattern activity.

The pharmacology of vertebrate spinal central pattern generators.

Central pattern generators are networks of neurons capable of generating an output pattern of spike activity in a relatively stereotyped, rhythmic pattern that has been found to underlie vital functions like respiration and locomotion. The central pattern generator for locomotion in vertebrates seems to share some basic building blocks. Activation and excitation of activity is driven by descending, sensory, and intraspinal glutamatergic neurons.

Discharge properties of neurons of the median raphe nucleus during hippocampal theta rhythm in the rat.

The serotonin (5-HT)-containing median raphe nucleus has been shown to be critically involved in the control of desynchronized (non theta) states of the hippocampal electroencephalogram (EEG). We examined the activity of 181 cells of the median raphe nucleus in the urethane-anesthetized rat and found that approximately 80% (145/181) of them showed changes in activity associated with changes in the hippocampal EEG. These cells were subdivided into theta-on (68%) and theta-off (32%) based on increased or decreased rates of activity with theta, respectively.