Biology subjects

Hammock, E.

Publications and source records attributed to Hammock, E..

4 recordsLinked to original sources

bioRxiv2022

Kidney collecting duct cells make vasopressin in response to NaCl induced hypertonicity

Vasopressin has traditionally been thought to be produced by the neurohypophyseal system and then released into the circulation where it regulates water homeostasis. The syndrome of inappropriate secretion of anti-diuretic hormone (vasopressin) raised the question if vasopressin could be produced outside of the brain and whether the kidney could be a source of vasopressin. We found that mouse and human kidneys expressed vasopressin mRNA. Using an antibody that detects the pre-pro-vasopressin, we found that immunoreactive pre-pro-vasopressin protein is found in mouse and human kidneys. Moreover, we found that murine collecting duct cells make biologically active vasopressin which increases in response to NaCl mediated hypertonicity, and that water restriction increases the abundance of kidney-derived vasopressin mRNA and protein expression in mouse kidneys. Thus, we provide evidence of biologically active production of kidney-derived vasopressin in kidney tubular epithelial cells.

physiology↗

bioRxiv2022

Altered PVN-to-CA2 hippocampal oxytocin pathway and reduced number of oxytocin-receptor expressing astrocytes in heart failure rats

Oxytocinergic actions within the hippocampal CA2 are important for neuromodulation, memory processing and social recognition. However, the source of the OTergic innervation, the cellular targets expressing the OT receptors (OTRs) and whether the PVN-to-CA2 OTergic system is altered during heart failure (HF), a condition recently associated with cognitive and mood decline, remains unknown. Using immunohistochemistry along with retrograde monosynaptic tracing, RNAscope and a novel OTR-Cre rat line, we show that the PVN (but not the supraoptic nucleus) is an important source of OTergic innervation to the CA2. These OTergic fibers were found in many instances in close apposition to OTR expressing cells within the CA2. Interestingly, while only a small proportion of neurons were found to express OTRs ([~]15%), this expression was much more abundant in CA2 astrocytes ([~]40%), an even higher proportion that was recently reported for astrocytes in the central amygdala. Using an established ischemic rat heart failure (HF) model, we found that HF resulted in robust changes in the PVN-to-CA2 OTergic system, both at the source and target levels. Within the PVN, we found an increased OT immunoreactivity, along with a diminished OTR expression in PVN neurons. Within the CA2 of HF rats, we observed a blunted OTergic innervation, along with a diminished OTR expression, which appeared to be restricted to CA2 astrocytes. Taken together, our studies highlight astrocytes as key cellular targets mediating OTergic PVN inputs to the CA2 hippocampal region. Moreover, provides the first evidence for an altered PVN-to-CA2 OTergic system in HF rats, which could potentially contribute to previously reported cognitive and mood impairments in this animal model.

neuroscience↗

bioRxiv2020

Acute neonatal oxytocin impacts hippocampal network development and restores adult social memory deficits in a mouse model of autism spectrum disorder.

Oxytocin is a master regulator of the social brain. In some animal models of autism, notably in Magel2 tm1.1Mus-deficient mice, peripheral administration of oxytocin in infancy improves social behaviors until adulthood. However, neither the mechanisms responsible for social deficits nor the mechanisms by which such oxytocin administration has long-term effects are known. Here, we aimed to clarify these oxytocin-dependent mechanisms focusing on social memory performance. We showed that Magel2tm1.1Mus-deficient mice present a deficit in social memory and studied the hippocampal circuits underlying this memory. We showed a co-expression of Magel2 and oxytocin-receptor in the dentate gyrus and CA2/CA3 hippocampal regions. Then, we demonstrated: an increase of the GABAergic activity of CA3-pyramidal cells associated with an increase in the quantity of oxytocin-receptors and of somatostatin interneurons. We also revealed a delay in the GABAergic development sequence in Magel2tm1.1Mus-deficient pups, linked to phosphorylation modifications of KCC2. Above all, we demonstrated the positive effects of subcutaneous administration of oxytocin in the mutant neonates, restoring neuronal alterations and social memory. Although clinical trials are debated, this study highlights the mechanisms by which peripheral oxytocin-administration in neonates impacts the brain and demonstrates the therapeutic value of oxytocin to treat infants with autism spectrum disorders.

neuroscience↗

bioRxiv2019

Oxytocin shapes spontaneous activity patterns in the developing visual cortex by activating somatostatin interneurons

Spontaneous network activity shapes emerging neuronal circuits during early brain development, however how neuromodulation influences this activity is not fully understood. Here, we report that the neuromodulator oxytocin powerfully shapes spontaneous activity patterns. In vivo, oxytocin strongly decreased the frequency and pairwise correlations of spontaneous activity events in visual cortex (V1), but not in somatosensory cortex (S1). This differential effect was a consequence of oxytocin only increasing inhibition in V1 and increasing both inhibition and excitation in S1. The increase in inhibition was mediated by the depolarization and increase in excitability of somatostatin+ (SST) interneurons specifically. Accordingly, silencing SST+ neurons pharmacogenetically fully blocked oxytocins effect on inhibition in vitro as well its effect on spontaneous activity patterns in vivo. Thus, oxytocin decreases the excitatory/inhibitory ratio and modulates specific features of V1 spontaneous activity patterns that are crucial for refining developing synaptic connections and sensory processing later in life.

neuroscience↗