Biology subjects

Eliava, M.

Publications and source records attributed to Eliava, M..

4 recordsLinked to original sources

bioRxiv2024

Oxytocin facilitates social behavior of female rats via selective modulation of interneurons in the medial prefrontal cortex

The hypothalamic neuropeptide oxytocin is best known for its prosocial behavioral effects. However, the precise anatomical and cellular targets for oxytocin in the cortex during social behavior remain elusive. Here we show that oxytocin neurons project directly to the medial prefrontal cortex where evoked axonal oxytocin release facilitates social behaviors in adult female rats. In conjunction, we report that local oxytocin receptor-expressing (OTR+) cells are predominantly interneurons, whose activation promotes social interaction. Notably, this prosocial effect persists even under physiological challenge (hunger), pointing to a dedicated prosocial circuit capable of overriding primary survival drives. We further demonstrate that activation of these OTR+ interneurons inhibits principal cells specifically projecting to the basolateral amygdala, thus providing a putative mechanism of selective oxytocin action in this sociability-promoting cortical network.

neuroscience↗

bioRxiv2023

Excitatory neurons in stratum radiatum provide an alternative pathway for excitation flow that escapes perisomatic inhibition

For over half a century, it has been postulated that the internal excitatory circuit in the hippocampus consists of three relay stations. Excitation arrives from the entorhinal cortex to the DG granule cells, is transmitted through the mossy fibers to CA3 pyramidal cells, and is then transmitted through Schaffer collaterals to CA1 pyramidal neurons. In all three structures (DG, CA3 and CA1), the activity of the excitatory neurons involved in the synaptic transmission of excitation are under the control of inhibitory basket neurons that are recruited into network activity via feed-forward and feed-back excitation. However, in the late 90s "stratum radiatum giant cells" were described as a novel type of neuron with the anatomical features of excitatory cells. Since then, the role of these cells in the hippocampal circuitry has not been well understood. Here, using optogenetic and electrophysiological techniques we characterized the functional location of these neurons within the hippocampal network. We show that: (i) the main excitatory drive to giant excitatory neurons in stratum radiatum (ExNR) comes via Schaffer collaterals; (ii) within the CA1 field, ExNR are not directly connected with local pyramidal cells, but provide massive and efficient excitatory input to parvalbumin positive (PV+) interneurons; (iii) ExNR are reciprocally innervated by bistratified cells, but not inhibited by backet interneurons; (iv) the efficiency of ExNR excitation to PV+ interneurons is sufficient for a single ExNR action potential to trigger massive inhibition of downstream CA1 pyramidal cells. Taken together, our data shows that ExNR constitute an alternative pathway of excitation for CA1 interneurons that avoids the burden of perisomatic inhibition.

neuroscience↗

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

Oxytocin Acts on Astrocytes in the Central Amygdala to Promote a Positive Emotional State

Oxytocin orchestrates social and emotional behaviors through modulation of neural circuits in brain structures such as the central amygdala (CeA). The long-standing dogma is that oxytocin signaling in the central nervous system occurs exclusively via direct actions on neurons. However, several findings over the last decades showed that astrocytes actively participate in the modulation of neuronal circuits. Here, we investigate the degree of astrocytes involvement in oxytocin functions. Using astrocyte specific gain and loss of function approaches, we demonstrate that CeA astrocytes not only directly respond to oxytocin, but are actually necessary for its effects on neuronal circuits and ultimately behavior. Our work identifies astrocytes as a crucial cellular substrate underlying the promotion of a positive emotional state by oxytocin. These results further corroborate that astrocytes are key regulators of neuronal circuits activity by responding to specific neuropeptidergic inputs, and opens up new perspectives to understand how neuromodulators gate brain functions.

neuroscience↗