Repeated exposure to multiple concurrent stressors alters visual processing in the adult posterior parietal cortex.

Chronic stress is well known to erode cognitive functions. Yet, our understanding of how repeated stress exposure impacts one of the fundamental bases of cognition: sensory processing, remains limited. The posterior parietal cortex (PPC) is a high order visual region, known for its role in visually guided decision making, multimodal integration, attention, and working memory.

Extracellular ATP Neurotransmission and Nicotine Sex-Specifically Modulate Habenular Neuronal Activity in Adolescence.

The recent increase in the use of nicotine products by teenagers has revealed an urgent need to better understand the impact of nicotine on the adolescent brain. Here, we sought to examine the actions of extracellular ATP as a neurotransmitter and to investigate whether ATP and nicotinic signaling interact during adolescence. With the GRAB (G-protein-coupled receptor activation-based ATP sensor), we first demonstrated that nicotine induces extracellular ATP release in the medial habenula, a brain region involved in nicotine aversion and withdrawal.

Practical considerations in an era of multicolor optogenetics.

The ability to control synaptic communication is indispensable to modern neuroscience. Until recently, only single-pathway manipulations were possible due to limited availability of opsins activated by distinct wavelengths. However, extensive protein engineering and screening efforts have drastically expanded the optogenetic toolkit, ushering in an era of multicolor approaches for studying neural circuits.

A Comprehensive, Affordable, Open-Source Hardware-Software Solution for Flexible Implementation of Complex Behaviors in Head-Fixed Mice.

Experiments that take advantage of head-fixed behavioral tasks have been a staple of systems neuroscience research for half a century. More recently, rodents came to the forefront of these efforts, primarily because of the rich experimental possibilities afforded by modern genetic tools. There is, however, a considerable barrier to entering this field, requiring expertise in engineering, hardware and software development, and significant time and financial commitment.

Cell-type-specific integration of feedforward and feedback synaptic inputs in the posterior parietal cortex.

The integration of feedforward (sensory) and feedback (top-down) neuronal signals is a principal function of the neocortex. Yet, we have limited insight into how these information streams are combined by individual neurons. Using a two-color optogenetic strategy, we found that layer 5 pyramidal neurons in the posterior parietal cortex receive monosynaptic dual innervation, combining sensory inputs with top-down signals.

To deconvolve, or not to deconvolve: Inferences of neuronal activities using calcium imaging data.

Background: With the increasing popularity of calcium imaging in neuroscience research, choosing the right methods to analyze calcium imaging data is critical to address various scientific questions. Unlike spike trains measured using electrodes, fluorescence intensity traces provide an indirect and noisy measurement of the underlying neuronal activities. The observed calcium traces are either analyzed directly or deconvolved to spike trains to infer neuronal activities.

Sex-dependent long-term effects of prepubescent stress on the posterior parietal cortex.

Adolescence is a time of intense cortical development and a period of heightened sensitivity to insult. To determine how sex affects the short- and long-term outcomes of early-adolescent stress exposure, we subjected prepubescent (postnatal day 30) male and female mice to repeated multiple concurrent stressors (RMS). In the posterior parietal cortex (PPC), RMS caused the elimination of excitatory synapses in deeper layers while inhibitory synapse density was predominantly diminished in superficial layers.

Repeated Exposure to Multiple Concurrent Stresses Induce Circuit Specific Loss of Inputs to the Posterior Parietal Cortex.

Severe loss of excitatory synapses in key brain regions is thought to be one of the major mechanisms underlying stress-induced cognitive impairment. To date, however, the identity of the affected circuits remains elusive. Here we examined the effect of exposure to repeated multiple concurrent stressors (RMS) on the connectivity of the posterior parietal cortex (PPC) in adolescent male mice.

Simultaneous mesoscopic and two-photon imaging of neuronal activity in cortical circuits.

Spontaneous and sensory-evoked activity propagates across varying spatial scales in the mammalian cortex, but technical challenges have limited conceptual links between the function of local neuronal circuits and brain-wide network dynamics. We present a method for simultaneous cellular-resolution two-photon calcium imaging of a local microcircuit and mesoscopic widefield calcium imaging of the entire cortical mantle in awake mice. Our multi-scale approach involves a microscope with an orthogonal axis design where the mesoscopic objective is oriented above the brain and the two-photon objective is oriented horizontally, with imaging performed through a microprism.

Ketamine disrupts neuromodulatory control of glutamatergic synaptic transmission.

A growing body of literature has demonstrated the potential for ketamine in the treatment of major depression. Sub-anesthetic doses produce rapid and sustained changes in depressive behavior, both in patients and rodent models, associated with reorganization of glutamatergic synapses in the prefrontal cortex (PFC). While ketamine is known to regulate N-methyl-D-aspartate (NMDA) -type glutamate receptors (NMDARs), the full complement of downstream cellular consequences for ketamine administration are not well understood.

New Aspects of the Contribution of ER to SOCE Regulation: The Role of the ER and ER-Plasma Membrane Junctions in the Regulation of SOCE.

The junctions between the endoplasmic reticulum and the plasma membrane are essential platforms for the activation of store-operated Ca influx. These junctions have specific dimensions and are nonuniformly distributed in polarized cells. The mechanisms involved in the formation of the junctions are currently undergoing vigorous investigation, and significant progress was attained in this research area during the last 10 years.

Developmental Dysfunction of VIP Interneurons Impairs Cortical Circuits.

GABAergic interneurons play important roles in cortical circuit development. However, there are multiple populations of interneurons and their respective developmental contributions remain poorly explored. Neuregulin 1 (NRG1) and its interneuron-specific receptor ERBB4 are critical genes for interneuron maturation.

Projection-Specific Visual Feature Encoding by Layer 5 Cortical Subnetworks.

Primary neocortical sensory areas act as central hubs, distributing afferent information to numerous cortical and subcortical structures. However, it remains unclear whether each downstream target receives a distinct version of sensory information. We used in vivo calcium imaging combined with retrograde tracing to monitor visual response properties of three distinct subpopulations of projection neurons in primary visual cortex.

Glutamate Receptor Modulation Is Restricted to Synaptic Microdomains.

A diverse array of neuromodulators governs cellular function in the prefrontal cortex (PFC) via the activation of G-protein-coupled receptors (GPCRs). However, these functionally diverse signals are carried and amplified by a relatively small assortment of intracellular second messengers. Here, we examine whether two distinct Gαi-coupled neuromodulators (norepinephrine and GABA) act as redundant regulators of glutamatergic synaptic transmission.

Stress Impairs Prefrontal Cortical Function via D1 Dopamine Receptor Interactions With Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels.

Background: Psychiatric disorders such as schizophrenia are worsened by stress, and working memory deficits are often a central feature of illness. Working memory is mediated by the persistent firing of prefrontal cortical (PFC) pyramidal neurons. Stress impairs working memory via high levels of dopamine D1 receptor (D1R) activation of cyclic adenosine monophosphate signaling, which reduces PFC neuronal firing.

Compartmentalization of GABAergic inhibition by dendritic spines.

γ-aminobutyric acid-mediated (GABAergic) inhibition plays a critical role in shaping neuronal activity in the neocortex. Numerous experimental investigations have examined perisomatic inhibitory synapses, which control action potential output from pyramidal neurons. However, most inhibitory synapses in the neocortex are formed onto pyramidal cell dendrites, where theoretical studies suggest they may focally regulate cellular activity.

Cellular geography of IP3 receptors, STIM and Orai: a lesson from secretory epithelial cells.

Pancreatic acinar cells exhibit a remarkable polarization of Ca2+ release and Ca2+ influx mechanisms. In the present brief review, we discuss the localization of channels responsible for Ca2+ release [mainly IP3 (inositol 1,4,5-trisphosphate) receptors] and proteins responsible for SOCE (store-operated Ca2+ entry). We also place these Ca2+-transporting mechanisms on the map of cellular organelles in pancreatic acinar cells, and discuss the physiological implications of the cellular geography of Ca2+ signalling.

InsP₃receptors and Orai channels in pancreatic acinar cells: co-localization and its consequences.

Orai1 proteins have been recently identified as subunits of SOCE (store-operated Ca²⁺ entry) channels. In primary isolated PACs (pancreatic acinar cells), Orai1 showed remarkable co-localization and co-immunoprecipitation with all three subtypes of IP₃Rs (InsP₃ receptors). The co-localization between Orai1 and IP₃Rs was restricted to the apical part of PACs.

Calmodulin protects against alcohol-induced pancreatic trypsinogen activation elicited via Ca2+ release through IP3 receptors.

Alcohol abuse is a major global health problem, but there is still much uncertainty about the mechanisms of action. So far, the effects of ethanol on ion channels in the plasma membrane have received the most attention. We have now investigated actions on intracellular calcium channels in pancreatic acinar cells.

EGR1 Is a target for cooperative interactions between cholecystokinin and leptin, and inhibition by ghrelin, in vagal afferent neurons.

Food intake is regulated by signals from peripheral organs, but the way these are integrated remains uncertain. Cholecystokinin (CCK) from the intestine and leptin from adipocytes interact to inhibit food intake. Our aim was to examine the hypothesis that these interactions occur at the level of vagal afferent neurons via control of the immediate early gene EGR1.

Ribosome-free terminals of rough ER allow formation of STIM1 puncta and segregation of STIM1 from IP(3) receptors.

Store-operated Ca(2+) entry is a ubiquitous mechanism that prevents the depletion of endoplasmic reticulum (ER) calcium. A reduction of ER calcium triggers translocation of STIM proteins, which serve as calcium sensors in the ER, to subplasmalemmal puncta where they interact with and activate Orai channels. In pancreatic acinar cells, inositol 1,4,5-trisphosphate (IP(3)) receptors populate the apical part of the ER.

Pancreatic protease activation by alcohol metabolite depends on Ca2+ release via acid store IP3 receptors.

Toxic alcohol effects on pancreatic acinar cells, causing the often fatal human disease acute pancreatitis, are principally mediated by fatty acid ethyl esters (non-oxidative products of alcohol and fatty acids), emptying internal stores of Ca(2+). This excessive Ca(2+) liberation induces Ca(2+)-dependent necrosis due to intracellular trypsin activation. Our aim was to identify the specific source of the Ca(2+) release linked to the fatal intracellular protease activation.

ATP depletion induces translocation of STIM1 to puncta and formation of STIM1-ORAI1 clusters: translocation and re-translocation of STIM1 does not require ATP.

Depletion of the endoplasmic reticulum (ER) calcium store triggers translocation of stromal interacting molecule one (STIM1) to the sub-plasmalemmal region and formation of puncta-structures in which STIM1 interacts and activates calcium channels. ATP depletion induced the formation of STIM1 puncta in PANC1, RAMA37, and HeLa cells. The sequence of events triggered by inhibition of ATP production included a rapid decline of ATP, depletion of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) and a slow calcium leak from the ER followed by formation of STIM1 puncta.