Biology subjects

Gomes, J. I.

Publications and source records attributed to Gomes, J. I..

3 recordsLinked to original sources

bioRxiv2026

Enrichment experience improves hippocampal sparse coding via inhibitory circuit plasticity

Environmental enrichment enhances hippocampus-dependent learning and memory, yet the underlying circuit mechanisms remain largely unknown. Here we combined miniscope calcium imaging during spatial exploration with synaptic circuit analysis in hippocampal slices to determine how enrichment experience alters hippocampal network dynamics. Prolonged enrichment reduced average firing rates and immediate early gene expression in CA1 pyramidal cells, while increasing peak firing and spatial selectivity. Population activity was sparser and more diverse, resulting in a higher Gini index. Circuit analysis revealed enhanced excitatory drive onto both pyramidal cells and somatostatin (SOM) interneurons, together with a strengthened SOM-mediated feedback inhibition onto pyramidal cells. Suppressing SOM interneurons occluded the enrichment-induced augmentation of sparsity and Gini index and prevented improvements in hippocampus-dependent learning. These findings demonstrate that environmental enrichment dynamically enhances hippocampal sparse coding through potentiation of SOM-mediated feedback inhibition, linking experience-dependent inhibitory plasticity to enhanced memory performance.

neuroscience↗

bioRxiv2021

Unexpected short- and long-term effects of chronic adolescent HU-210 exposure on emotional behavior

Chronic adolescent cannabinoid receptor agonist exposure has been shown to lead to persistent increases in depressive-like behaviors. This has been a key obstacle to the development of cannabinoid-based therapeutics. However, most of the published work has been performed with only three compounds, namely {Delta}9-tetrahydrocannabinol, CP55,940 and WIN55,212-2. Hypothesizing that different compounds may lead to distinct outcomes, we herein used the highly potent CB1R/CB2R full agonist HU-210, and first aimed at replicating cannabinoid-induced long-lasting effects, by exposing adolescent female Sprague-Dawley rats to increasing doses of HU-210, for 11 days and testing them at adulthood, after a 30-day drug washout. Surprisingly, HU-210 did not significantly impact adult anxious- or depressive-like behaviors. We then tested whether chronic adolescent HU-210 treatment resulted in short-term (24h) alterations in depressive-like behavior. Remarkably, HU-210 treatment simultaneously induced marked antidepressant- and prodepressant-like responses, in the modified forced swim (mFST) and sucrose preference tests (SPT), respectively. Hypothesizing that mFST results were a misleading artifact of HU-210-induced behavioral hyperreactivity to stress, we assessed plasmatic noradrenaline and corticosterone levels, under basal conditions and following an acute swim-stress episode. Notably, we found that while HU-210 did not alter basal noradrenaline or corticosterone levels, it greatly augmented the stress-induced increase in both. Our results show that, contrary to previously studied cannabinoid receptor agonists, HU-210 does not induce persisting depressive-like alterations, despite inducing marked short-term increases in stress-induced reactivity. By showing that not all cannabinoid receptor agonists may induce long-term negative effects, these results hold significant relevance for the development of cannabinoid-based therapeutics.

pharmacology and toxicology↗

bioRxiv2021

Astrocytes are implicated in BDNF-mediated enhancement of hippocampal long-term potentiation

It is known that astrocytes, by the Ca2+-dependent release of gliotransmitters, which then act in pre- and post-synaptic receptors, modulate neuronal transmission and plasticity. Thus, hippocampal {theta}-burst long-term potentiation (LTP), which is a form of synaptic plasticity, can be modulated by astrocytes, since these cells release gliotransmitters that are crucial for the maintenance of LTP. Therefore, in this study, we hypothesized that the facilitatory action of BDNF upon LTP would involve astrocytes. To address that possibility, fEPSP recordings were performed in CA3-CA1 area of hippocampal slices from three different experimental models: Wistar rats where astrocytic metabolism was selectively reduced by a gliotoxin, the DL-fluoricitric acid (FC), IP3R2-/- mice, which lack IP3R2-mediated Ca2+-signaling in astrocytes and dn-SNARE transgenic mice, in which the SNARE-dependent release of gliotransmittersis impaired. For the three models we observed that the astrocytic impairment abolished the excitatory BDNF effect upon hippocampal LTP, only while inducing LTP with a mild {theta}-burst stimulation paradigm. The present data shows for the first time that astrocytes play an active role in the facilitatory action of BDNF upon LTP, depending on stimulation paradigm.

neuroscience↗