Biology subjects

Csicsvari, J.

Publications and source records attributed to Csicsvari, J..

8 recordsLinked to original sources

bioRxiv2026

The ovarian cycle and estradiol modulate cortical network state and auditory entrainment in mice and women

The human brain is remarkably dynamic, continuously adapting to internal and external signals across rapid and protracted timescales. While both male and female brains are influenced by sex hormones to drive adaptive behavioural and physiological changes, the ovarian cycle in female mammals represents a conserved naturalistic model to understand how hormones such as estradiol (E2) alter cellular and network states to shape brain function. To understand whether and how the ovarian cycle influences sensory cortical processing, we investigated cortical network activity at rest and upon auditory stimulation across the ovarian cycle in mice and human subjects. We recorded EEG activity in men and women and intracortical local field potentials in male and female mice. Female participants were tested during two phases of their ovarian cycle characterized by low E2 levels (early follicular phase in women; late estrus in mice) and high E2 levels (late follicular phase in women; proestrus in mice). Across species, high endogenous or exogenous estradiol was associated with a steeper aperiodic power spectral slope, indicating decreased excitatory/inhibitory drive and attenuated auditory entrainment following a 40Hz stimulation. At the single-cell level, high E2 selectively increased the baseline and sustained 40-Hz firing of putative fast-spiking interneurons while reducing their temporal coherence during both spontaneous and stimulus-evoked activity, suggesting that E2 enhances inhibitory tone, while disrupting the temporal coordination of inhibitory networks. Altogether, these findings demonstrate that estradiol dynamically modulates cortical network states and auditory responsiveness. This underscores the necessity of investigating hormone-brain coupling as an evolutionarily conserved model essential for yielding translational insights into sex-specific neurobiology.

neuroscience↗

bioRxiv2026

Representational Dynamics in the Hippocampus and Medial Prefrontal Cortex during Learning and Task Mastery

While the medial prefrontal cortex (mPFC) interacts with the hippocampus to support learning and consolidation, how its neural representations evolve remains unclear. We recorded population activity from CA1 and the mPFC as rats trained on radial maze tasks over weeks. Low-dimensional mPFC manifolds generated using UMAP or PCA embeddings initially tracked session progression, showing within-session drift. As animals gained task familiarity, this temporal tracking weakened; mPFC manifolds differentiated specific arms, mirroring hippocampal representations. Arm discriminability was selectively enhanced at locations requiring spatial choices, but weakened when such demands were absent. These findings demonstrate that systems consolidation does not uniformly promote cortical generalization. Instead, the mPFC may slowly refine representations in response to specific task demands to support tailored task schemas.

neuroscience↗

bioRxiv2026

The scaling behavior of hippocampal activity in sleep/rest predicts spatial memory performance

In the hippocampus, reactivation of spatial memories during sleep enhances consolidation and recall. However, network dynamics may independently influence memory retention. We applied the Phenomenological Renormalization Group to CA1 neuronal activity in rats during sleep/rest epochs surrounding a spatial learning task. The scaling exponent of activity variance (), assessed either before or after learning, predicted subsequent recall performance independently of reactivation. The prediction model was transferable across subjects, suggesting that it is a robust biomarker of learning ability. Single-cell features, such as burst propensity and intrinsic timescales, correlated with and memory, predicted retention even when controlling for these factors. Our results identified a link between scale-free circuit dynamics and memory stabilization, suggesting that the tuning of the underlying dynamical regime near criticality is a key determinant of memory longevity. Targeted modulation of these collective states could offer new avenues for memory enhancement.

neuroscience↗

bioRxiv2023

Sleep stages antagonistically modulate reactivation drift

Hippocampal reactivation of waking neuronal assemblies in sleep is a key initial step of systems consolidation. Nevertheless, it is unclear whether reactivated assemblies are static or whether they reorganize gradually over prolonged sleep. Here, we tracked reactivated CA1 assembly patterns over [~]20 hours of sleep/rest periods and related them to assemblies seen before or after in a spatial learning paradigm. We found that reactivated assembly patterns were gradually transformed and started to resemble those seen in the subsequent recall session. Periods of rapid eye movement (REM) sleep and non-REM (NREM) had antagonistic roles: while NREM accelerated the assembly drift, REM countered it. Moreover, only a subset of rate-changing pyramidal cells contributed to the drift, while stable firing rate cells maintained unaltered reactivation patterns. Our data suggest that prolonged sleep promotes the spontaneous reorganization of spatial assemblies, which can contribute to daily cognitive map changes or encoding new learning situations.

neuroscience↗

bioRxiv2023

Phase-locking of hippocampal CA3 neurons to distal CA1 theta oscillations selectively predicts memory performance

How the coordination of neuronal spiking activity and brain rhythms between hippocampal subregions supports memory function remains elusive. We studied interregional coordination of CA3 neuronal spiking activity with CA1 theta oscillations by recording electrophysiological signals along the proximodistal axis of the hippocampus in rats performing a high memory demand recognition memory task adapted from humans. We found that CA3 population spiking activity occurs preferentially at the peak of distal CA1 theta oscillations only when animals recalled previously encountered stimuli. In addition, decoding analyses revealed that only population cell firing of proximal CA3 together with that of distal CA1 can predict memory performance in the present non-spatial task. Overall, our work demonstrates an important role of the synchronization of CA3 neuronal activity with CA1 theta oscillations for successful recognition memory.

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bioRxiv2022

Entorhinal layer 6b subplate neurons govern spatial learning and memory

The mammalian hippocampal formation (HF) plays a key role in several higher brain functions, such as spatial coding, learning and memory. Its simple circuit architecture is often viewed as a "trisynaptic loop", processing input originating from the superficial layers of the entorhinal cortex (EC) in a linear fashion, and sending it back to its deeper layers. Here, we show that contrary to this canonical view, excitatory neurons in the deepest layer of the mouse EC, exhibiting the unique morphology and molecular profile of layer 6b cortical subplate neurons (SPNs), project to all sub-regions comprising the HF, with a preference towards CA3 pyramidal neurons, and receive input from the CA1, thalamus and claustrum. Furthermore, their output is characterized by unique slow-decaying excitatory post-synaptic currents (EPSCs), capable of driving plateau-like potentials in their target cells. Optogenetic inhibition of the EC-6b pathway markedly affects spatial coding in CA1 pyramidal neurons, while cell ablation impairs not only acquisition of new spatial memories, but also degradation of previously acquired ones. Our results provide the first evidence of a functional role for the cortical layer 6b neurons in the adult brain and elucidate a critical novel element determining cortico-hippocampal activity patterns.

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bioRxiv2021

The generalized spatial representation in the prefrontal cortex is inherited from the hippocampus

Hippocampal and neocortical neural activity is modulated by the position of the individual in space. While hippocampal neurons provide the basis for a spatial map, prefrontal cortical neurons generalize over environmental features. Whether these generalized representations result from a bidirectional interaction with, or are mainly derived from hippocampal spatial representations is not known. By examining simultaneously recorded hippocampal and medial prefrontal neurons, we observed that prefrontal spatial representations show a delayed coherence with hippocampal ones. We also identified subpopulations of cells in the hippocampus and medial prefrontal cortex that formed functional cross-area couplings; these resembled the optimal connections predicted by a probabilistic model of spatial information transfer and generalization. Moreover, cross-area couplings were strongest and had the shortest delay preceding spatial decision-making. Our results suggest that generalized spatial coding in the medial prefrontal cortex is inherited from spatial representations in the hippocampus, and that the routing of information can change dynamically with behavioral demands.

neuroscience↗

bioRxiv2021

The structure of hippocampal CA1 interactions optimizes spatial coding across experience

Although much is known about how single neurons in the hippocampus represent an animals position, how cell-cell interactions contribute to spatial coding remains poorly understood. Using a novel statistical estimator and theoretical modeling, both developed in the framework of maximum entropy models, we reveal highly structured cell-to-cell interactions whose statistics depend on familiar vs. novel environment. In both conditions the circuit interactions optimize the encoding of spatial information, but for regimes that differ in the signal-to-noise ratio of their spatial inputs. Moreover, the topology of the interactions facilitates linear decodability, making the information easy to read out by downstream circuits. These findings suggest that the efficient coding hypothesis is not applicable only to individual neuron properties in the sensory periphery, but also to neural interactions in the central brain.

neuroscience↗