Biology subjects

Lopez-Cabezon, C.

Publications and source records attributed to Lopez-Cabezon, C..

3 recordsLinked to original sources

bioRxiv2026

A Reproducible Cortical Model of Focal Epileptiform Activity with a Multi-Biomarker Analysis Pipeline

The development of surface-based therapeutic strategies, including extracranial illumination and epicortical electrical or optoelectronic neuromodulation, requires experimental models in which focal pathological activity can be generated and monitored within an accessible cortical region. Here, we established an acute cortical model of focal epileptiform activity in anesthetized mice based on local microinjection of 4-aminopyridine (4-AP) into the barrel cortex. This preparation provides precise spatial and temporal control of the epileptiform focus while enabling simultaneous electrophysiological sampling across cortical depth. To objectively characterize the induced activity, we implemented a Python-based analysis pipeline integrating complementary electrophysiological biomarkers, including oscillatory power, multi-unit activity, pathological fast ripples (250-650 Hz), and epileptiform bursts. Local 4-AP administration produced robust increases in gamma (30-100 Hz) power, multi-unit firing (MUA), fast ripple and burst activity. Pharmacological sensitivity of the framework was evaluated using carbamazepine, which robustly attenuated 4-AP-induced increases in all biomarkers. Together, this study provides a reproducible experimental and analytical framework for investigating focal cortical epileptiform activity and for the future evaluation of pharmacological, optical, and electrical interventions targeting superficial cortical networks.

neuroscience↗

bioRxiv2025

Cellular mechanisms underlying the pro-cognitive effects of serotonin 5-HT7 receptors in a mouse model of schizophrenia

Serotonin 5-HT7 receptors (5-HT7Rs) have emerged as promising targets for treating cognitive and affective disturbances in schizophrenia and other neuropsychiatric disorders, yet their cellular substrates and circuit-level mechanisms remain poorly defined. Here, we combined immunohistochemistry, multisite electrophysiology, and behavioral assays to investigate how 5-HT7Rs modulate hippocampal-prefrontal pathways in healthy mice and in a subchronic phencyclidine (sPCP) model of cognitive and negative symptoms in schizophrenia. We found that 5-HT7Rs are abundantly expressed in both excitatory and inhibitory neurons of the dorsal hippocampus (dHPC) and medial prefrontal cortex (mPFC), with high co-expression in PV and SST interneurons ([~]80% in dHPC; 55% PV and 75% SST in mPFC). In healthy mice, systemic 5-HT7R activation with the agonist AS-19 suppressed neuronal activity and synchrony within dHPC (CA1) - mPFC (PL) pathways, reducing theta and high-gamma power, theta-gamma coupling in CA1, theta coherence, and CA1[->]PL directional connectivity, consistent with recruitment of inhibitory microcircuits. The similarity between 5-HT7R-mediated inhibition and the circuit effects we previously described for 5-HT1AR activation, together with evidence for 5-HT7R-5-HT1AR heterodimerization, suggests that these receptors act in concert to dynamically constrain hippocampal-prefrontal circuits. sPCP treatment induced persistent recognition-memory impairments, heightened anxiety-like behavior, and pathological high-frequency synchronization of hippocampal-prefrontal networks. Blockade of 5-HT7Rs with SB-269970 or the atypical antipsychotic lurasidone (but not lurasidone combined with AS-19) rescued memory performance, reduced anxiety-like behavior, and normalized aberrant high-frequency hypersynchrony, while enhancing CA1[->]PL theta signaling immediately before memory acquisition. Together, these findings indicate that 5-HT7R activation exerts potent inhibitory control over hippocampal-prefrontal pathways, likely via PV and SST interneurons, and suggest that 5-HT7R blockade constitutes a promising therapeutic strategy to restore excitation-inhibition balance and enhance neural communication within brain circuits crucial for cognition and mood regulation in neuropsychiatric disorders.

neuroscience↗

bioRxiv2023

Neural substrates of cognitive impairment in a NMDAR hypofunction mouse model of schizophrenia and rescue by risperidone

NMDAR hypofunction is a pathophysiological mechanism relevant for schizophrenia. Acute administration of the NMDAR antagonist phencyclidine (PCP) induces psychosis in patients and animals while subchronic PCP (sPCP) produces cognitive dysfunction for weeks. We investigated the neural correlates of memory and perceptual impairments in mice treated with sPCP and the rescuing abilities of the atypical antipsychotic drug risperidone administered daily for two weeks. We recorded neural activities in the medial prefrontal cortex (mPFC) and the dorsal hippocampus (dHPC) during memory acquisition, short-term, and long-term memory in the novel object recognition test and during auditory perception and mismatch negativity (MMN) and examined the effects of sPCP and sPCP followed by risperidone. We found that the information about the new object and its short-term storage were associated with mPFC[->]dHPC high gamma connectivity whereas long-term memory retrieval depended on dHPC[->]mPFC theta connectivity. sPCP impaired short-term and long-term memory, which was associated with increased mPFC and decreased dHPC neural network activities, and disrupted mPFC-dHPC connectivity. Risperidone rescued the memory deficits and attenuated hippocampal desynchronization. sPCP also impaired auditory perception and its neural correlates (evoked potentials and MMN) in the mPFC, which were also ameliorated by risperidone. Our study suggests that during NMDAR hypofunction the mPFC and the dHPC disconnect possibly underlying cognitive impairment in schizophrenia, and that risperidone targets this circuit to ameliorate cognitive abilities in patients.

neuroscience↗