Biology subjects

Hernandez, V. S.

Publications and source records attributed to Hernandez, V. S..

3 recordsLinked to original sources

bioRxiv2020

Vasopressin acts as a synapse organizer in limbic regions by boosting PSD95 and GluA1 expression

Hypothalamic arginine vasopressin (AVP)-containing magnocellular neurosecretory neurons (AVPMNN) emit collaterals to synaptically innervate limbic regions influencing learning, motivational behaviour, and fear responses. Here, we characterize the dynamics of expression changes of two key determinants for synaptic strength, the postsynaptic density (PSD) proteins AMPAR subunit GluA1 and PSD scaffolding protein 95 (PSD95), in response to in vivo manipulations of AVPMNN neuronal activation state, or exposure to exogenous AVP ex vivo. Both long term water deprivation in vivo, which powerfully upregulates AVPMNN metabolic activity, and exogenous AVP application ex vivo, in brain slices, significantly increased GluA1 and PSD95 expression measured by western blot, in brain regions reportedly receiving direct ascending innervations from AVPMNN (i.e., ventral hippocampus, amygdala and lateral habenula). In contrast, the visual cortex, a region not observed to receive AVPMNN projections, showed no such changes. Ex vivo application of V1a and V1b antagonists to ventral hippocampal slices ablated the AVP stimulated increase in postsynaptic protein expression measured by western blot. Using a modified expansion microscopy technique, we were able to quantitatively assess the significant augmentation of PSD95 and GLUA1 densities in subcellular compartments in locus coeruleus tyrosine hydroxylase immunopositive fibres, adjacent to AVP axon terminals. Our data strongly suggest that the AVPMNN ascending system plays a role in the regulation of the excitability of targeted neuronal circuits through upregulation of key post-synaptic density proteins corresponding to excitatory synapse. Supported by grantsUNAM-DGAPA-PAPIIT-IN200121 & CONACYT-CB-238744 (LZ); CONACYT A1-S-8731 (LIE); MH002386, NIMH, NIH, USA (LEE)

neuroscience↗

bioRxiv2020

Microglial synaptic pruning on axon initial segment of dentate granule cells: sexually dimorphic effects on fear response of adult rats subjected to early life stress

Axon initial segments (AIS) of dentate granule cells (GC) in hippocampus exhibit prominent spines during early development that are associated with microglial contacts. Here, we asked if developmental changes in axon initial segment spines (AISS) could be modified by neonatal maternal separation through stress hormones and microglial activation and examined the potential behavioral consequences. We examined AISS densities at postnatal day (PND) 15 and 50, using Golgi-Cox staining and anatomical analysis. Neuron-microglial interaction was assessed using antibodies against ankyrinG, PSD95 and Iba1, for AIS, AISS and microglia, respectively, in normally reared and neonatal maternally separated (MS) male and female rats. We observed a higher density of AISS in MS groups at both PND15 and PND50 compared to control. Effects were more pronounced in female than in male rats. AIS-associated microglia showed a hyper-ramified morphology and less co-localization with PSD95 in MS compared to normally reared animals at PND 15. An MS-like alteration in microglial morphology and synaptic pruning could be produced ex vivo by vasopressin application in acute hippocampal slices from normally reared animals. MS rats exhibited increased freezing behavior during auditory fear memory testing which, like effects on AISS density, was more pronounced in females than males. Freezing behavior was associated with Fos expression in dorsal and ventral dentate GC. In summary, AIS associated microglial activity is altered by MS. Sex differences in the long-term effects of MS on AISS density are penetrant to a behavioral phenotype of increased stimulus reactivity in adult female subjects.

neuroscience↗

bioRxiv2020

Behavioral role of PACAP signaling reflects its selective distribution in glutamatergic and GABAergic neuronal subpopulations

The neuropeptide PACAP, acting as a co-transmitter, increases neuronal excitability, which may enhance anxiety and arousal associated with threat conveyed by multiple sensory modalities. The distribution of neurons expressing PACAP and its receptor, PAC1, throughout the mouse nervous system was determined, in register with expression of glutamatergic and GABAergic neuronal markers, to develop a coherent chemoanatomical picture of PACAPs role in brain motor responses to sensory input. A circuit role for PACAP was tested by observing fos activation of brain neurons after olfactory threat cue in wild type and PACAP knockout mice. Neuronal activation, and behavioral response, were blunted in PACAP knock-out mice, accompanied by sharply down-regulated vesicular transporter expression in both GABAergic and glutamatergic neurons expressing PACAP and its receptor. This report signals a new perspective on the role of neuropeptide signaling in supporting excitatory and inhibitory neurotransmission in the nervous system within functionally coherent polysynaptic circuits.

neuroscience↗