Biology subjects

Sere, P.

Publications and source records attributed to Sere, P..

4 recordsLinked to original sources

bioRxiv2025

Heterogeneity of ictal firing during generalized seizures in the awake cortex

Cortico-thalamo-cortical oscillations are central to both normal and pathological brain activities and emerge from complex cortical and thalamic interactions. However, the specific activity of identified cortical neurons during the paroxysmal oscillations associated with absence seizures (ASs) in awake animals remains underexplored. The dominant narrative suggests that seizures indiscriminately disrupt cortical activity through generalized hyperexcitability, but direct evidence supporting this view is lacking. Here, we recorded single units from pyramidal neurons and different interneuron subtypes in the neocortex of two validated rodent models of absence epilepsy under awake, behaving conditions. We find that neurons maintain their firing rank order across interictal and ictal states, regardless of whether their ictal firing rate increases, decreases, or remains stable compared to the interictal phase. Rather than a random cortical takeover, ictal activity represents a scalable modulation of pre-existing network states. These results challenge the generalized hyperexcitability model and highlight the structured, heterogeneous nature of cortical activity during ASs, with implications for mechanistic understanding and targeted therapies.

neuroscience↗

bioRxiv2022

Higher-order thalamic nuclei facilitate the generalization and maintenance of spike-and-wave discharges in absence seizures

Spike-and-wave discharges (SWDs), generated by the cortico-thalamo-cortical (CTC) network, are pathological, large amplitude oscillations and the hallmark of absence seizures (ASs). SWDs begin in a cortical initiation network in both humans and animal models, including the Genetic Absence Epilepsy Rats from Strasbourg (GAERS), where it is located in the primary somatosensory cortex (S1). The behavioral manifestation of an AS occurs when SWDs spread from the cortical initiation site to the whole brain, however, the mechanisms behind this rapid propagation remain unclear. Here we investigated these processes beyond the principal CTC network, in higher-order (HO) thalamic nuclei (lateral posterior (LP) and posterior (PO) nuclei) since their diffuse connectivity and known facilitation of intracortical communications make these nuclei key candidates to support SWD generation and maintenance. In freely moving GAERS, multi-site LFP in LP, PO and multiple cortical regions revealed a novel feature of SWDs: during SWDs there are short periods (named SWD-breaks) when cortical regions far from S1, such the primary visual cortex (V1), become transiently unsynchronized from the ongoing EEG rhythm. Inactivation of HO nuclei with local muscimol injections or optogenetic perturbation of HO nuclei activity increased the occurrence of SWD-breaks and the former intervention also increased the SWD propagation-time from S1. The neural underpinnings of these findings were explored further by silicon probe recordings from single units of PO which uncovered two previously unknown groups of excitatory neurons based on their burst firing dynamics at SWD onset. Moreover, a switch from tonic to burst firing at SWD onset was shown to be an important feature since it was much less prominent for non-generalized events, i.e. SWDs that remained local to S1. Additionally, one group of neurons showed a reverse of this switch during SWD-breaks, demonstrating the importance of this firing pattern throughout the SWD. In summary, these results support the view that multiple HO thalamic nuclei are utilized at SWD onset and contribute to cortical synchrony throughout the paroxysmal discharge.

neuroscience↗

bioRxiv2021

Cell-type specific arousal-dependent modulation of thalamic activity in the lateral geniculate nucleus

State dependent thalamocortical activity is important for sensory coding, oscillations and cognition. The lateral geniculate nucleus (LGN) relays visual information to the cortex, but the state dependent spontaneous and visually evoked activity of LGN neurons in awake behaving animals remains controversial. Using a combination of pupillometry, extracellular and intracellular recordings from identified LGN neurons we show that thalamocortical neurons and interneurons are distinctly correlated to arousal forming two complementary coalitions. Intracellular recordings indicated that the membrane potential of LGN TC neurons was tightly correlated to fluctuations in pupil size. Inactivating the corticothalamic feedback to the LGN suppressed the arousal dependency of LGN neurons. Taken together our results show that LGN neuronal membrane potential and action potential output are dynamically linked to arousal dependent brain states in awake mice and this might have important functional implications.

neuroscience↗

bioRxiv2020

Disinhibition mediated by reciprocal hypothalamic and raphe GABAergic projections promotes wakefulness

The lateral hypothalamus (LH), together with multiple neuromodulatory systems of the brain, such as the dorsal raphe nucleus (DR), is implicated in arousal, yet interactions between these systems are just beginning to be explored. Using a combination of viral tracing, circuit mapping, electrophysiological recordings from identified neurons and combinatorial optogenetics in mice, we show that GABAergic neurons in the LH selectively inhibit GABAergic neurons in the DR resulting in increased firing of a substantial fraction of its neurons that ultimately promotes arousal. These DRGABA neurons are wake active and project to multiple brain areas involved in the control of arousal including the LH, where their specific activation potently influences local network activity leading to arousal from sleep. Our results show how mutual inhibitory projections between the LH and the DR promote wakefulness and suggest a complex arousal control by intimate interactions between long-range connections and local circuit dynamics.

neuroscience↗