Fine Chemo-anatomy of Hypothalamic Magnocellular Vasopressinergic System with an Emphasis on Ascending Connections for Behavioural Adaptation

et al. 2020

Preprint

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Hypothalamic arginine vasopressin (AVP)-containing magnocellular neurosecretory neurons (AVPMNN) emit collaterals to synaptically innervate limbic regions influencing learning, motivational behavior and fear responses. The purpose of the present work is to characterize the dynamics of expression changes of two postsynaptic density (PSD) proteins, AMPAR subunit GluA1 and PSD scaffolding protein 95 (PSD95), which are known to be key determinants for synaptic strength, in response to in vivo and ex vivo manipulations of AVPMNN neuronal activation state, or exposure to exogenous AVP, metabolites and some signaling pathway inhibitors. Both long term water deprivation in vivo, which powerfully upregulates AVPMNN activity, and exogenous APV application ex vivo in brain slices, increased GluA1 and PSD95 expression and enhanced neuronal excitability in ventral hippocampal CA1 pyramidal neurons. Involvement of PI3k signaling in AVP-dependent plasticity is suggested by blockade of both AVP-induced protein up-regulation and enhanced neuronal excitability by the PI3k blocker wortmannin in hippocampal slices. We interpret these results as part of vasopressin’s central effects on synaptic organization in limbic regions modulating the strength of a specific set of synaptic proteins in hypothalamic-limbic circuits.Supported by grantsUNAM-DGAPA-PAPIIT-IN216918 & CONACYT-CB-238744.

Section: Introductionmentioning

confidence: 76%

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

Zhang

Padilla‐Flores

et al. 2020

Preprint

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“…Note the clearly visible allocortical feature, three layers of the NLOT clearly visible. Da and Db show two magnocellular neurons, single-stained within the SON, that they emitted 3 main axons from soma or proximal dendrites and coursed medially (1), dorsally (2) and laterally (3) that could be followed and reconstructed using adjacent sections (see Fig. 4A).…”

Section: Figure 3 Anatomical Relationship and Interconnections Betwee...mentioning

confidence: 99%

“…This is because AVPMNNs have very well-defined roles as neurosecretory neurons that release vasopressin into the bloodstream for hormonally-driven osmotic regulation (hydromineral homeostasis), and as well, via dual projections within the brain parenchyma, release vasopressin as a neurotransmitter to affect limbic, hypothalamic, and other brain circuits that participate in behavioral prioritization responsive to competing homeostatic drives, i.e. allostasis (2) .…”

Section: Introductionmentioning

confidence: 99%

Nucleus of the lateral olfactory tract (NLOT): a hub linking water homeostasis-associated SON-AVP circuit and neocortical regions to promote social behavior under osmotic challenge

Hernández‐Pérez

Zetter

et al. 2022

Preprint

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Homeostatic challenges increase the drive for social interaction. The neural activity that prompts this motivation remains poorly understood. Here, we identify direct projections from hypothalamic supraoptic nucleus (SON) to the cortico-amygdalar nucleus of the lateral olfactory tract (NLOT). Dual in situ hybridization (DISH) with probes for PACAP, and VGLUT1, VGLUT2, V1a and V1b revealed a population of vasopressin-receptive PACAPergic neurons in NLOT layer 2 (NLOT2). Water deprivation (48 hours, WD48) increased sociability compared to euhydrated subjects, assessed with the three-chamber social interaction test (3CST). Fos expression immunohistochemistry showed NLOT and its main efferent regions had further increases in rats subjected to WD48+3CST. These regions strongly expressed PAC1 mRNA. Microinjections of AVP into NLOT produced similar changes in sociability to water deprivation, and these were reduced by co-injection of V1a or V1b antagonists along with AVP. We conclude that during challenge to water homeostasis, there is a recruitment of a glutamatergic-multi-peptidergic cooperative circuit that promotes social behavior.

“…Subsequently, AVP was localized to Gray type I synapses, usually corresponding to glutamatergic (excitatory) neurotransmission, 8 in hippocampus, 9 amygdala, 10 lateral habenula, 11 and locus coeruleus (LC) 12 . These observations cemented the notion that AVP could act within the brain as well as in the periphery through AVP release from the same neurons, which therefore integrated regulation of homeostatic (hydromineral balance) and allostatic (behavioural) physiology within a single type of neurohormonal/neuropeptide cell 13,14 …”

Section: Introductionmentioning

confidence: 95%

“…12 These observations cemented the notion that AVP could act within the brain as well as in the periphery through AVP release from the same neurons, which therefore integrated regulation of homeostatic (hydromineral balance) and allostatic (behavioural) physiology within a single type of neurohormonal/neuropeptide cell. 13,14 Despite the plethora of observations detailing AVP actions at hippocampal and other cognitive hubs in the brain (vide supra), the cellular mechanisms by which AVP potentiates neuronal excitability are not known. AVP-containing dense core vesicles (AVP+ DCV) have been observed at excitatory synaptic active zones, docked onto the presynaptic membrane, suggesting that vasopressin modulation of neurotransmission may occur at the level of the synapse itself within limbic regions such as hippocampus, 9 amygdala, 10 lateral habenula, 11 and LC.…”

Section: Introductionmentioning

confidence: 99%

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

Zhang

Padilla‐Flores

et al. 2022

J Neuroendocrinology

Self Cite

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 as measured by western blotting, in brain regions reportedly receiving direct ascending innervations from AVPMNN (i.e., ventral hippocampus, amygdala and lateral habenula). By 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 blotting. 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 postsynaptic density proteins corresponding to excitatory synapses.