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.

Interaction of reelin with amyloid precursor protein promotes neurite outgrowth.

The processing of amyloid precursor protein (APP) to Abeta is an important event in the pathogenesis of Alzheimer's disease, but the physiological function of APP is not well understood. Our previous work has shown that APP processing and Abeta production are regulated by the extracellular matrix protein Reelin. In the present study, we examined whether Reelin interacts with APP, and the functional consequences of that interaction in vitro. Using coimmunoprecipitation, we found that Reelin interacted with APP through the central domain of Reelin (repeats 3-6) and the E1 extracellular domain of APP. Reelin increased cell surface levels of APP and decreased endocytosis of APP in hippocampal neurons in vitro. In vivo, Reelin levels were increased in brains of APP knock-out mice and decreased in APP-overexpressing mice. RNA interference knockdown of APP decreased neurite outgrowth in vitro and prevented Reelin from increasing neurite outgrowth. Knock-out of APP or Reelin decreased dendritic arborization in cortical neurons in vivo, and APP overexpression increased dendritic arborization. APP and Reelin have previously been shown to promote neurite outgrowth through interactions with integrins. We confirmed that APP interacted with alpha3beta1 integrin, and alpha3beta1 integrin altered APP trafficking and processing. Addition of an alpha3beta1 integrin antibody prevented APP and Reelin-induced neurite outgrowth. These findings demonstrate that Reelin interacts with APP, potentially having important effects on neurite development.

Differential regulation of telencephalic pallial-subpallial boundary patterning by Pax6 and Gsh2.

In the embryonic telencephalon, the pallial-subpallial boundary (PSB) separates the dorsal Pax6+ pallium from the ventral Gsh2+ subpallium. Previous studies have revealed that this region is a source of cells that will populate both the olfactory bulb and basal telencephalic limbic system. However, the level of progenitor cell heterogeneity and developmental genetic regulation of this progenitor region remains to be fully elucidated. In this study we carried out a comprehensive analysis of gene expression patterns at the PSB, in addition to an examination of the combinatorial function of Pax6 and Gsh2 in the specification of the PSB. First, we reveal that the PSB is comprised of a complex mix of molecularly distinct progenitor pools. In addition, by analysis of single Sey, Gsh2, and Sey/Gsh2 double mutant mice, we demonstrate that both Pax6 and Gsh2 are directly required for major aspects of PSB progenitor specification. Our analysis also reveals that the establishment of the epidermal growth factor receptor positive lateral cortical stream migratory route to the basal telencephalon is Pax6 dependent. Thus, in addition to their well-characterized cross-repressive roles in dorsal/ventral patterning our analyses reveal important novel functions of Gsh2 and Pax6 in the regulation of PSB progenitor pool specification and patterning.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Cell migration along the lateral cortical stream to the developing basal telencephalic limbic system.

During embryogenesis, the lateral cortical stream (LCS) emerges from the corticostriatal border (CSB), the boundary between the developing cerebral cortex and striatum. The LCS is comprised of a mix of pallial- and subpallial-derived neural progenitor cells that migrate to the developing structures of the basal telencephalon, most notably the piriform cortex and amygdala. Using a combination of in vitro and in vivo approaches, we analyzed the timing, composition, migratory modes, origin, and requirement of the homeodomain-containing transcription factor Gsh2 (genomic screened homeobox 2) in the development of this prominent migratory stream. We reveal that Pax6 (paired box gene 6)-positive pallial-derived and Dlx2 (distal-less homeobox 2)-positive subpallial-derived subpopulations of LCS cells are generated in distinct temporal windows during embryogenesis. Furthermore, our data indicate the CSB border not only is comprised of separate populations of pallial- and subpallial-derived progenitors that contribute to the LCS but also a subpopulation of cells coexpressing Pax6 and Dlx2. Moreover, despite migrating along a route outlined by a cascade of radial glia, the Dlx2-positive population appears to migrate primarily in an apparent chain-like manner, with LCS migratory cells being generated locally at the CSB with little contribution from other subpallial structures such as the medial, lateral, or caudal ganglionic eminences. We further demonstrate that the generation of the LCS is dependent on the homeodomain-containing gene Gsh2, revealing a novel requirement for Gsh2 in telencephalic development.