Biology subjects

Llamosas, N.

Publications and source records attributed to Llamosas, N..

4 recordsLinked to original sources

bioRxiv2026

Differential Effects of 5-HT7 Receptor Signaling in the Noradrenergic System in a Rat Model of Treatment-Resistant Depression

IntroductionTreatment-resistant depression (TRD) is a major clinical challenge, and its neurobiological basis remains unclear. The locus coeruleus (LC), a key noradrenergic hub, shows altered activity in TRD models, and serotonergic 5-HT7 receptors have emerged as potential modulators of this circuit. MethodsWe assessed the impact of 5-HT7 receptor activation on LC function in Wistar Kyoto rats, an established TRD model, using in vivo extracellular recordings, in vitro patch-clamp assays, and receptor expression analysis. ResultsSystemic administration of AS19, a selective 5-HT7 receptor agonist, increased LC neuronal firing in both strains, with a significantly greater effect in Wistar Kyoto rats. This response was prevented by a 5-HT7 antagonist confirming receptor specificity. Glutamatergic blockade altered AS19 effects in a strain-dependent manner, whereas in vitro assays revealed no differential postsynaptic modulation and similar presynaptic inhibition across groups. Western blot analysis showed elevated 5-HT7 receptor expression in the LC, ventral hippocampus, and amygdala of Wistar Kyoto rats, alongside reduced expression in the prefrontal cortex. ConclusionThese findings indicate that 5-HT7 receptor activation exerts complex, circuit-dependent modulation of LC activity, influenced by glutamatergic and serotonergic inputs. Enhanced receptor expression in limbic regions and altered LC responsiveness may contribute to TRD pathophysiology and highlight 5-HT7 signaling as a promising target for novel therapeutic strategies.

neuroscience↗

bioRxiv2024

Traumatic brain injury enhances the intrinsic excitation and excitatory transmission of granule cells

Traumatic brain injury (TBI) leads to a wide range of long-lasting physical and cognitive impairments. Changes in neuronal excitability and synaptic functions in the hippocampus have been proposed to underlie cognitive alterations. The dentate gyrus (DG) acts as a "gatekeeper" of hippocampal information processing and as a filter of excessive or aberrant input activity. In this study, we investigated the effects of controlled cortical impact, a model of TBI, on the excitability of granule cells (GCs) and excitatory postsynaptic transmission in the DG at three time points, 3 days, 15 days and 4 months after the injury. Our results indicate that changes in the short term are related to intrinsic properties, while changes in the long term are more related to input and synaptic activity, in agreement with the notion that TBI-related pathology courses with an acute phase and a later long-term secondary phase. A biphasic response, a reduction in the shorter term and an increase in the long term, was found in TBI neurons in the frequency of sEPSC. These changes correlated with a loss of complexity in the pattern of the synaptic input, an alteration that could therefore play a role in the chronic and recurrent TBI-asssociated hyperexcitation.

neuroscience↗

bioRxiv2020

Human SYNGAP1 Regulates the Development of Neuronal Activity by Controlling Dendritic and Synaptic Maturation

SYNGAP1 is a major genetic risk factor for global developmental delay, autism spectrum disorder, and epileptic encephalopathy. De novo loss-of-function variants in this gene cause a neurodevelopmental disorder defined by cognitive impairment, social-communication disorder, and early-onset seizures. Cell biological studies in mouse and rat neurons have shown that Syngap1 regulates developing excitatory synapse structure and function, with loss-of-function variants driving formation of larger dendritic spines and stronger glutamatergic transmission. However, studies to date have been limited to mouse and rat neurons. Therefore, it remains unknown how SYNGAP1 loss-of-function impacts the development and function of human neurons. To address this, we employed CRISPR/Cas9 technology to ablate SYNGAP1 protein expression in neurons derived from a human induced pluripotent stem cell line (hiPSC). Reducing SynGAP protein expression in developing hiPSC-derived neurons enhanced dendritic morphogenesis, leading to larger neurons compared to those derived from isogenic controls. Consistent with larger dendritic fields, we also observed a greater number of morphologically defined excitatory synapses in cultures containing these neurons. Moreover, neurons with reduced SynGAP protein had stronger excitatory synapses and expressed synaptic activity earlier in development. Finally, distributed network spiking activity appeared earlier, was substantially elevated, and exhibited greater bursting behavior in SYNGAP1 null neurons. We conclude that SYNGAP1 regulates the postmitotic maturation of human neurons made from hiPSCs, which influences how activity develops within nascent neural networks. Alterations to this fundamental neurodevelopmental process may contribute to the etiology of SYNGAP1-related disorders.

neuroscience↗

bioRxiv2020

Syngap1 Dynamically Regulates the Fine-Scale Reorganization of Cortical Circuits in Response to Sensory Experience

Experience induces complex, neuron-specific changes in population activity within sensory cortex circuits. However, the mechanisms that enable neuron-specific changes within cortical populations remain unclear. To explore the idea that synapse strengthening is involved, we studied fine-scale cortical plasticity in Syngap1 mice, a neurodevelopmental disorder model useful for linking synapse biology to circuit functions. Repeated functional imaging of the same L2/3 somatosensory cortex neurons during single whisker experience revealed that Syngap1 selectively regulated the plasticity of a low-active, or "silent", neuronal subpopulation. Syngap1 also regulated spike-timing-dependent synaptic potentiation and experience-mediated in vivo synapse bouton formation, but not synaptic depression or bouton elimination in L2/3. Adult re-expression of Syngap1 restored plasticity of "silent" neurons, demonstrating that this gene controls dynamic cellular processes required for population-specific changes to cortical circuits during experience. These findings suggest that abnormal experience-dependent redistribution of cortical population activity may contribute to the etiology of neurodevelopmental disorders.

neuroscience↗