Neurocognitive and Synaptic Potentiation Deficits Are Mitigated by Inhibition of HIF1a Signaling following Intermittent Hypoxia in Rodents.

Highlighted Research Paper: A HIF1a-Dependent Pro-Oxidant State Disrupts Synaptic Plasticity and Impairs Spatial Memory in Response to Intermittent Hypoxia. Alejandra Arias-Cavieres, Maggie A. Khuu, Chinwendu U. Nwakudu, Jasmine E. Barnard, Gokhan Dalgin and Alfredo J. Garcia III.

Astrocytes Function as an Intermediate for Retrograde Endocannabinoid Signaling in the Suprachiasmatic Nucleus to Influence Circadian Clock Timing.

Highlighted Research Paper: Cannabinoid Signaling Recruits Astrocytes to Modulate Presynaptic Function in the Suprachiasmatic Nucleus. Lauren M. Hablitz, Ali N. Gunesch, Olga Cravetchi, Michael Moldavan and Charles N. Allen.

Pharmacological Inactivation of Medial Prefrontal Cortex Does Not Support Dichotomous "Go/Stop" Roles for Dorsal and Ventral Subdivisions in Natural Reward Seeking in Rats.

Highlighted Research Paper: Differential Effects of Dorsal and Ventral Medial Prefrontal Cortex Inactivation during Natural Reward Seeking, Extinction, and Cue-Induced Reinstatement. Jessica P. Caballero, Garrett B. Scarpa, Luke Remage-Healey, David E. Moorman.

Transplanted Human Induced Pluripotent Stem Cell-Derived Neurons Wire and Fire with Balanced Excitation-Inhibition in Rat Cortex.

Highlighted Research Paper: Neurons Derived from Human Induced Pluripotent Stem Cells Integrate into Rat Brain Circuits and Maintain Both Excitatory and Inhibitory Synaptic Activities. Xiling Yin, Jin-Chong Xu, Gun-sik Cho, Chulan Kwon, Ted M. Dawson and Valina L. Dawson.

Does Prenatal Exposure to Maternal Inflammation Causes Sex Differences in Schizophrenia-Related Behavioral Outcomes in Adult Rats?

Highlighted Research Paper: Maternal Immune Activation during Pregnancy Alters the Behavior Profile of Female Offspring of Sprague Dawley Rats, by Brittney R. Lins, Wendie N. Marks, Nadine K. Zabder, Quentin Greba, and John G. Howland.

Differential Effects of Chronic Alcohol Consumption on Cortical and Subcortical Brain Volume in Adolescent Nonhuman Primates.

Highlighted Research Paper: Chronic Alcohol Drinking Slows Brain Development in Adolescent and Young Adult Nonhuman Primates, by Tatiana A. Shnitko, Zheng Liu, Xiaojie Wang, Kathleen A. Grant, and Christopher D. Kroenke.

Ultrasonic Vocalizations Emitted during Defensive Behavior Alter the Influence of the Respiratory Rhythm on Brain Oscillatory Dynamics in the Fear Circuit of Rats.

Highlighted Research Paper: New Insights from 22-kHz Ultrasonic Vocalizations to Characterize Fear Responses: Relationship with Respiration and Brain Oscillatory Dynamics, by Maryne Dupin, Samuel Garcia, Julie Boulanger-Bertolus, Nathalie Buonviso, and Anne-Marie Mouly.

Concurrent Medial Prefrontal Cortex and Dorsal Hippocampal Activity Is Required for Estradiol-Mediated Effects on Object Memory and Spatial Memory Consolidation.

Highlighted Research Paper: Chemogenetic Suppression of Medial Prefrontal-Dorsal Hippocampal Interactions Prevents Estrogenic Enhancement of Memory Consolidation in Female Mice by, Jennifer J. Tuscher, Lisa R. Taxier, Jayson C. Schalk, Jacqueline M. Haertel, and Karyn M. Frick.

Estrogen-Dominant Ovarian Cycle Stages Are Associated with Neural Network Dysfunction and Cognitive and Behavioral Deficits in the hAPP-J20 Mouse Model of Alzheimer's Disease.

Highlighted Research Paper: Ovarian Cycle Stages Modulate Alzheimer-Related Cognitive and Brain Network Alterations in Female Mice, by Lauren Broestl, Kurtresha Worden, Arturo J. Moreno, Emily J. Davis, Dan Wang, Bayardo Garay, Tanya Singh, Laure Verret, Jorge J. Palop, and Dena B. Dubal.

Potential Protein Target to Therapeutically Restore Positive Mood States in Depression.

Highlighted Research Paper: Disorders of the Nervous System Highlighted Research Paper: p11 in Cholinergic Interneurons of the Nucleus Accumbens Is Essential for Dopamine Responses to Rewarding Stimuli, by Y. Hanada, Y. Kawahara, Y. N. Ohnishi, T. Shuto, M. Kuroiwa, N. Sotogaku, P. Greengard, Y. Sagi, and A. Nishi.

Partial, Rather than Full, BACE1 Inhibition May Be a Better Therapeutic Strategy for Alzheimer's Disease Due to Effects of Complete Loss of BACE1 Activity on Adult Hippocampal Neurogenesis.

Highlighted Research Paper: BACE1 Regulates Proliferation and Neuronal Differentiation of Newborn Cells in the Adult Hippocampus in Mice by, Zena K. Chatila, Eunhee Kim, Clara Berlé, Enjana Bylykbashi, Alexander Rompala, Mary K. Oram, Drew Gupta, Sang Su Kwak, Young Hye Kim, Doo Yeon Kim, Se Hoon Choi, and Rudolph E. Tanzi.

Changes in Functional Brain Connectivity Highlight the Importance of a Baseline Measurement and Multiple Imaging Sessions for Cocaine Abstinence Studies.

Highlighted Research Paper: Functional Connectivity of Chronic Cocaine Use Reveals Progressive Neuroadaptations in Neocortical, Striatal, and Limbic Networks by, Caitlin A. Orsini, Luis M. Colon-Perez, Sara C. Heshmati, Barry Setlow, and Marcelo Febo.

How Do Drosophila Stay Awake during the Daytime? Dopaminergic Neurons Are Inhibited by the Pigment Dispersing Factor Signaling Pathway to Promote Wakefulness.

Highlighted Research Paper: Wakefulness Is Promoted during Day Time by PDFR Signalling to Dopaminergic Neurons in Drosophila melanogaster, by, Sheetal Potdar and Vasu Sheeba.

Spontaneous Brain Oscillations Induce Neuronal Excitability Changes That Affect Subjective Perception, Rather Than Decision-Making Strategy.

Highlighted Research Paper: Moment-to-Moment Fluctuations in Neuronal Excitability Bias Subjective Perception Rather than Strategic Decision-Making, by Luca Iemi and Niko A. Busch.

Olig1 and Olig2 triplication causes developmental brain defects in Down syndrome.

Over-inhibition is thought to be one of the underlying causes of the cognitive deficits in Ts65Dn mice, the most widely used model of Down syndrome. We found a direct link between gene triplication and defects in neuron production during embryonic development. These neurogenesis defects led to an imbalance between excitatory and inhibitory neurons and to increased inhibitory drive in the Ts65Dn forebrain. We discovered that Olig1 and Olig2, two genes that are triplicated in Down syndrome and in Ts65Dn mice, were overexpressed in the Ts65Dn forebrain. To test the hypothesis that Olig triplication causes the neurological phenotype, we used a genetic approach to normalize the dosage of these two genes and thereby rescued the inhibitory neuron phenotype in the Ts65Dn brain. These data identify seminal alterations during brain development and suggest a mechanistic relationship between triplicated genes and these brain abnormalities in the Ts65Dn mouse.

Sonic hedgehog expressing and responding cells generate neuronal diversity in the medial amygdala.

BACKGROUND: The mammalian amygdala is composed of two primary functional subdivisions, classified according to whether the major output projection of each nucleus is excitatory or inhibitory. The posterior dorsal and ventral subdivisions of the medial amygdala, which primarily contain inhibitory output neurons, modulate specific aspects of innate socio-sexual and aggressive behaviors. However, the development of the neuronal diversity of this complex and important structure remains to be fully elucidated. RESULTS: Using a combination of genetic fate-mapping and loss-of-function analyses, we examined the contribution and function of Sonic hedgehog (Shh)-expressing and Shh-responsive (Nkx2-1+ and Gli1+) neurons in the medial amygdala. Specifically, we found that Shh- and Nkx2-1-lineage cells contribute differentially to the dorsal and ventral subdivisions of the postnatal medial amygdala. These Shh- and Nkx2-1-lineage neurons express overlapping and non-overlapping inhibitory neuronal markers, such as Calbindin, FoxP2, nNOS and Somatostatin, revealing diverse fate contributions in discrete medial amygdala nuclear subdivisions. Electrophysiological analysis of the Shh-derived neurons additionally reveals an important functional diversity within this lineage in the medial amygdala. Moreover, inducible Gli1CreER(T2) temporal fate mapping shows that early-generated progenitors that respond to Shh signaling also contribute to medial amygdala neuronal diversity. Lastly, analysis of Nkx2-1 mutant mice demonstrates a genetic requirement for Nkx2-1 in inhibitory neuronal specification in the medial amygdala distinct from the requirement for Nkx2-1 in cerebral cortical development. CONCLUSIONS: Taken together, these data reveal a differential contribution of Shh-expressing and Shh-responding cells to medial amygdala neuronal diversity as well as the function of Nkx2-1 in the development of this important limbic system structure.

Emx1-lineage progenitors differentially contribute to neural diversity in the striatum and amygdala.

In the developing mammalian basal telencephalon, neural progenitors from the subpallium generate the majority of inhibitory medium spiny neurons (MSNs) in the striatum, while both pallial- and subpallial-derived progenitors contribute to excitatory and inhibitory neuronal diversity in the amygdala. Using a combination of approaches, including genetic fate mapping, cell birth dating, cell migration assays, and electrophysiology, we find that cells derived from the Emx1 lineage contribute to two distinct neuronal populations in the mature basal forebrain: inhibitory MSNs in the striatum and functionally distinct subclasses of excitatory neurons in the amygdala. Our cell birth-dating studies reveal that these two populations are born at different times during early neurogenesis, with the amygdala population born before the MSNs. In the striatum, Emx1-lineage neurons represent a unique subpopulation of MSNs: they are disproportionately localized to the dorsal striatum, are found in dopamine receiving, reelin-positive patches, and are born throughout striatal neurogenesis. In addition, our data suggest that a subpopulation of these Emx1-lineage cells originate in the pallium and subsequently migrate to the developing striatum and amygdala. Our intersectional fate-mapping analysis further reveals that Emx1-lineage cells that coexpress Dlx exclusively generate MSNs but do not contribute to the excitatory neurons in the amygdala. Thus, both the timing of neurogenesis and differential combinatorial gene expression appear to be key determinants of striatal versus amygdala fate decisions of Emx1-lineage cells.