Biology subjects

Koszeghy, A.

Publications and source records attributed to Koszeghy, A..

3 recordsLinked to original sources

bioRxiv2025

Reduced inhibition, bursting, and accelerated oscillations drive early hippocampal hyperactivity in Alzheimer's disease

Early hippocampal hyperactivity is a well-documented yet poorly defined phenomenon in Alzheimers disease (AD). While reported in both patients and animal models, its functional manifestations and underlying neurophysiological mechanisms in vivo remain unclear. Here, we address this gap using in vivo high-resolution patch-clamp, high-throughput single-unit, and local field recordings in young amyloidopathy mice, at a stage when A{beta} remains largely soluble. We uncover previously unidentified cellular mechanisms in vivo, characterised by reduced inhibitory synaptic input, hypoactivity of fast-spiking interneurons, and enhanced bursting in pyramidal neurons. At the network level, we reveal accelerated hippocampal oscillations, marked by increased theta and beta power, a departure from the conventional view of oscillation slowing in AD. Mechanistically, this acceleration stems from strengthened synchrony of excitatory currents at higher frequencies and an overall reduction in oscillation-associated inhibitory currents. Our findings provide the first direct in vivo evidence linking early hippocampal hyperactivity to specific synaptic transmission and network dysfunctions, resolving a long-standing ambiguity. Moreover, we propose accelerated oscillations in the hippocampus as a functional biomarker for early AD and a potential therapeutic target for restoring network stability before cognitive decline occurs.

neuroscience↗

bioRxiv2023

Action-outcome based flexible behavior requires medial prefrontal cortex lead and its enhanced functional connectivity with dorsomedial striatum

Cognitive flexibility plays a key role in ensuring an individuals survival, and its deficit is a key symptom in many mental conditions and neurodegenerative diseases. The prefrontal cortex and striatum are both essential to cognitive flexibility. However, how the prefrontal cortex and striatum communicate with each other to enable flexible decision-making is not well understood. Competing theories are raised, debating on which structure among these two leads the role in detecting and representing the new circumstances for a change, giving largely opposing predictions on neural activities in the prefrontal cortex and striatum during flexible behavior. To address this question, we trained head-restrained mice to perform an action-outcome based dynamic foraging task and simultaneously recorded single-neuron activities in the medial prefrontal cortex (mPFC) and dorsomedial striatum (DMS). In this task, the animal chooses one of two actions to obtain reward. The animal is guided only by previous reward outcomes. We report that mPFC but not DMS activity stores information about prior reward history. A large fraction of both mPFC and DMS neurons activity represents the difference in reward probability between two alternative options, namely the perceived reward probability difference (PRPD), a key decision variable that prescribes which subsequent choice to make. We find that mPFC neural activities track the change of PRPD earlier and faster than those in the DMS, and functional connectivity between mPFC and DMS increases with reducing overall reward proportion.

neuroscience↗

bioRxiv2023

Low-threshold, high-resolution, chronically stable intracortical microstimulation by ultraflexible electrodes

Intracortical microstimulation (ICMS) enables applications ranging from neuroprosthetics to causal circuit manipulations. However, the resolution, efficacy, and chronic stability of neuromodulation is often compromised by the adverse tissue responses to the indwelling electrodes. Here we engineer ultraflexible stim-Nanoelectronic Threads (StimNETs) and demonstrate low activation threshold, high resolution, and chronically stable ICMS in awake, behaving mouse models. In vivo two-photon imaging reveals that StimNETs remain seamlessly integrated with the nervous tissue throughout chronic stimulation periods and elicit stable, focal neuronal activation at low currents of 2 A. Importantly, StimNETs evoke longitudinally stable behavioral responses for over eight months at markedly low charge injection of 0.25 nC/phase. Quantified histological analysis show that chronic ICMS by StimNETs induce no neuronal degeneration or glial scarring. These results suggest that tissue-integrated electrodes provide a path for robust, long-lasting, spatially-selective neuromodulation at low currents which lessen risks of tissue damage or exacerbation of off-target side-effects.

neuroscience↗