Effects of Passive Avoidance Training on Calcium Flux in Chick Forebrain.

Calcium flux via voltage sensitive calcium channels (VSCC) was studied after passive avoidance training in the day-old chick. Intracellular free calcium concentration [Ca2+]i, after depolarisation with 70mM KC1> was measured using the calcium chelator fiira-2/AM in the crude membrane preparations from the IMHV and LPO of chicks. Experiments showed a significant increase in KCl-stimulated [Ca2+]i in the left IMHV of birds tested immediately after training compared to quiet birds (Q) and water trained birds (W). This increase was sustained in the left IMHV of birds tested 30 minutes after training. There was no significant difference between any of the groups of birds tested at later times. There was no significant increase in KCl-stimulated [Ca2+]i in the right IMHV of trained birds at any of the times tested. Significant elevation in KCl-stimulated [Ca2+]iwas also detected, in both the left and right LPO, of birds tested 5 minutes after training; which was still evident in birds tested 10 minutes after training. There was no significant difference between any of the treatment groups in the left or right LPO at any of the other times tested. Addition of different VSCC antagonists; such as co-conotoxin GVIA (N-type blocker), ω-conotoxin MVHC (N/P/Q-type blocker), nimodipine (L-type blocker), and co-agatoxin IVA (P-type blocker), were all shown to inhibit KCl-stimulated [Ca2+]i elevation in the crude membrane preparation from the IMHV of untrained chicks. Addition of ω-conotoxin GVIA, nimodipine or co-conotoxin MVHC into the crude membranes from the left or right IMHV of chicks, tested immediately after training, showed greater inhibition in the left IMHV of trained birds compared to Q- and W-birds. There was no difference in inhibition in the right IMHV between any of the treatment groups. The GABAergic receptors, GABAA and GABAB both inhibited KCl-stimulated [Ca2+]i elevation in crude membranes prepared from the IMHV of untrained chicks. Furthermore, the GABAB receptor antagonists were shown to exhibit some atypical properties. GABAB receptors were shown to evoke greater inhibition on KCl-stimulated [Ca2+]i elevation in crude membranes prepared from the IMHV of chicks tested 30 minutes after training compared to untrained birds and birds that were tested 5 minutes after training

Abnormal Sleep Signals Vulnerability to Chronic Social Defeat Stress.

There is a tight association between mood and sleep as disrupted sleep is a core feature of many mood disorders. The paucity in available animal models for investigating the role of sleep in the etiopathogenesis of depression-like behaviors led us to investigate whether prior sleep disturbances can predict susceptibility to future stress. Hence, we assessed sleep before and after chronic social defeat (CSD) stress. The social behavior of the mice post stress was classified in two main phenotypes: mice susceptible to stress that displayed social avoidance and mice resilient to stress. Pre-CSD, mice susceptible to stress displayed increased fragmentation of Non-Rapid Eye Movement (NREM) sleep, due to increased switching between NREM and wake and shorter average duration of NREM bouts, relative to mice resilient to stress. Logistic regression analysis showed that the pre-CSD sleep features from both phenotypes were separable enough to allow prediction of susceptibility to stress with >80% accuracy. Post-CSD, susceptible mice maintained high NREM fragmentation while resilient mice exhibited high NREM fragmentation, only in the dark. Our findings emphasize the putative role of fragmented NREM sleep in signaling vulnerability to stress

Select cognitive deficits in Vasoactive Intestinal Peptide deficient mice

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Class I HDAC Inhibition Blocks Cocaine-Induced Plasticity Through Targeted Changes in Histone Methylation

Induction of histone acetylation in the nucleus accumbens (NAc), a key brain reward region, promotes cocaine-induced alterations in gene expression. Histone deacetylases (HDACs) tightly regulate the acetylation of histone tails, but little is known about the functional specificity of different HDAC isoforms in the development and maintenance of cocaine-induced plasticity, and prior studies of HDAC inhibitors report conflicting effects on cocaine-elicited behavioral adaptations. Here, we demonstrate that specific and prolonged blockade of HDAC1 in NAc of mice increased global levels of histone acetylation, but also induced repressive histone methylation and antagonized cocaine-induced changes in behavior, an effect mediated in part via a chromatin-mediated suppression of GABAA receptor subunit expression and inhibitory tone on NAc neurons. Our findings suggest a novel mechanism by which prolonged and selective HDAC inhibition can alter behavioral and molecular adaptations to cocaine and inform the development of novel therapeutics for cocaine addiction

Erratum: Author Correction: Midbrain Circuit Regulation of Individual Alcohol Drinking Behaviors in Mice (Nature Communications (2017) 8 1 (2220))

The original version of this Article contained an error in the spelling of the author Scott Edwards, which was incorrectly given as Scott Edward. This has now been corrected in both the PDF and HTML versions of the Article

Midbrain circuit regulation of individual alcohol drinking behaviors in mice

Alcohol-use disorder (AUD) is the most prevalent substance-use disorder worldwide. There is substantial individual variability in alcohol drinking behaviors in the population, the neural circuit mechanisms of which remain elusive. Utilizing in vivo electrophysiological techniques, we find that low alcohol drinking (LAD) mice have dramatically higher ventral tegmental area (VTA) dopamine neuron firing and burst activity. Unexpectedly, VTA dopamine neuron activity in high alcohol drinking (HAD) mice does not differ from alcohol naive mice. Optogenetically enhancing VTA dopamine neuron burst activity in HAD mice decreases alcohol drinking behaviors. Circuit-specific recordings reveal that spontaneous activity of nucleus accumbens-projecting VTA (VTA-NAc) neurons is selectively higher in LAD mice. Specifically activating this projection is sufficient to reduce alcohol consumption in HAD mice. Furthermore, we uncover ionic and cellular mechanisms that suggest unique neuroadaptations between the alcohol drinking groups. Together, these data identify a neural circuit responsible for individual alcohol drinking behaviors

Odor Fear Conditioning Modifies Piriform Cortex Local Field Potentials Both during Conditioning and during Post-Conditioning Sleep

BACKGROUND: Sleep plays an active role in memory consolidation. Sleep structure (REM/Slow wave activity [SWS]) can be modified after learning, and in some cortical circuits, sleep is associated with replay of the learned experience. While the majority of this work has focused on neocortical and hippocampal circuits, the olfactory system may offer unique advantages as a model system for exploring sleep and memory, given the short, non-thalamic pathway from nose to primary olfactory (piriform cortex), and rapid cortex-dependent odor learning. METHODOLOGY/PRINCIPAL FINDINGS: We examined piriform cortical odor responses using local field potentials (LFPs) from freely behaving Long-Evans hooded rats over the sleep-wake cycle, and the neuronal modifications that occurred within the piriform cortex both during and after odor-fear conditioning. We also recorded LFPs from naïve animals to characterize sleep activity in the piriform cortex and to analyze transient odor-evoked cortical responses during different sleep stages. Naïve rats in their home cages spent 40% of their time in SWS, during which the piriform cortex was significantly hypo-responsive to odor stimulation compared to awake and REM sleep states. Rats trained in the paired odor-shock conditioning paradigm developed enhanced conditioned odor evoked gamma frequency activity in the piriform cortex over the course of training compared to pseudo-conditioned rats. Furthermore, conditioned rats spent significantly more time in SWS immediately post-training both compared to pre-training days and compared to pseudo-conditioned rats. The increase in SWS immediately after training significantly correlated with the duration of odor-evoked freezing the following day. CONCLUSIONS/SIGNIFICANCE: The rat piriform cortex is hypo-responsive to odors during SWS which accounts for nearly 40% of each 24 hour period. The duration of slow-wave activity in the piriform cortex is enhanced immediately post-conditioning, and this increase is significantly correlated with subsequent memory performance. Together, these results suggest the piriform cortex may go offline during SWS to facilitate consolidation of learned odors with reduced external interference