Biology subjects

Tzilivaki, A.

Publications and source records attributed to Tzilivaki, A..

7 recordsLinked to original sources

bioRxiv2026

Local inhibitory topology dictates the spatial compartmentalization of hippocampal sharp-wave ripples

Hippocampal sharp-wave ripples (SWRs) are essential for memory consolidation and represent among the most synchronous oscillatory events in the brain. Yet, despite their capacity for widespread synchronization, SWRs frequently remain confined to discrete hippocampal domains, revealing a paradox between global coordination and local autonomy. Here, by analysing existing in vivo recordings with an experimentally constrained three-dimensional biophysical model, we show that inhibitory activity and inhibitory topology serve fundamentally distinct functions. Whereas perisomatic inhibition gates SWR generation and dendritic inhibition regulates the strength and spectral properties of ripple oscillations, the spatial organization of inhibitory connectivity establishes local computational domains that enable autonomous ripple generators to coexist. Together, our findings identify a spatial dimension of inhibition, in which inhibitory activity governs the emergence and dynamics of SWRs, while inhibitory topology determines their spatial organization and autonomy.

neuroscience↗

bioRxiv2024

Bimodal dendritic processing in basket cells drives distinct memory-related oscillations

Neuronal oscillations are crucial for organizing distinct memory stages and behavioral states, yet the precise cellular mechanisms through which interneurons shape these dynamics remain incompletely understood. We propose and computationally explore a novel link between the nonlinear dendritic integration modes of parvalbumin-positive fast-spiking basket cells (PV+ FSBCs) and the modulation of hippocampal oscillations. Employing biophysical circuit level modeling, we test the hypothesis that PV+ FSBCs can flexibly adapt their firing patterns and influence rhythms, independent of gross changes in synaptic input quantity, by selectively engaging either their supralinear or sublinear dendritic branches. Specifically, supralinear dendrites promote high-frequency oscillations and reduce the excitation/inhibition (E/I) balance in the circuit, whereas sublinear dendrites enhance slow oscillatory power and elevate the E/I balance. This bimodal dendritic strategy provides PV+ FSBCs with an energy efficient mechanism to regulate circuit and oscillatory dynamics without necessitating large scale increases in synaptic drive. Our findings thereby uncover a previously unrecognized role for PV+ FSBC dendritic computations in regulating memory-related oscillations, offering new, experimentally testable hypotheses into the subcellular mechanisms that govern hippocampal rhythm generation.

neuroscience↗

bioRxiv2024

A dendritic substrate for temporal diversity of cortical inhibition

In the mammalian neocortex, GABAergic interneurons (INs) inhibit cortical networks in profoundly different ways. The extent to which this depends on how different INs process excitatory signals along their dendrites is poorly understood. Here, we reveal that the functional specialization of two major populations of cortical INs is determined by the unique association of different dendritic integration modes with distinct synaptic organization motifs. We found that somatostatin (SST)-INs exhibit NMDAR-dependent dendritic integration and uniform synapse density along the dendritic tree. In contrast, dendrites of parvalbumin (PV)-INs exhibit passive synaptic integration coupled with proximally enriched synaptic distributions. Theoretical analysis shows that these two dendritic configurations result in different strategies to optimize synaptic efficacy in thin dendritic structures. Yet, the two configurations lead to distinct temporal engagement of each IN during network activity. We confirmed these predictions with in vivo recordings of IN activity in the visual cortex of awake mice, revealing a rapid and linear recruitment of PV-INs as opposed to a long-lasting integrative activation of SST-INs. Our work reveals the existence of distinct dendritic strategies that confer distinct temporal representations for the two major classes of neocortical INs and thus dynamics of inhibition.

neuroscience↗

bioRxiv2023

Gamma-Oscillation Plasticity Is Mediated by Parvalbumin Interneurons

Understanding the plasticity of neuronal networks is an emerging field of (patho-)physiological research, yet little is known about the underlying cellular mechanisms. Gamma-oscillations (30 - 80 Hz), a biomarker of cognitive performance, require and potentiate glutamatergic transmission onto parvalbumin-positive interneurons (PVIs), suggesting an interface for cell-to-network plasticity. In ex vivo local field potential recordings, we demonstrate long-term potentiation of hippocampal gamma-power. Gamma-potentiation obeys established rules of PVI plasticity, requiring calcium-permeable AMPA receptors (CP-AMPARs) and metabotropic glutamate receptors (mGluRs). A microcircuit model of CA3 gamma-oscillations predicts CP-AMPAR plasticity onto PVIs critically outperforms pyramidal cell plasticity in increasing gamma-power and completely accounts for gamma-potentiation. We re-affirm this ex vivo in three PVI-targeting animal models, demonstrating that gamma-potentiation requires PVI-specific metabotropic signaling via a Gq/PKC-pathway comprising mGluR5 and a Gi-sensitive, PKA-dependent pathway. Gamma-activity dependent, metabotropically mediated CP-AMPAR plasticity on PVIs may serve as a guiding principle in understanding network plasticity in health and disease.

neuroscience↗

bioRxiv2021

A Locus Coeruleus- dorsal CA1 dopaminergic circuit modulates memory linking

Individual memories are often linked so that the recall of one triggers the recall of another. For example, contextual memories acquired close in time can be linked, and this is known to depend on temporary increase in excitability that drive the overlap between dorsal CA1 (dCA1) hippocampal ensembles encoding the linked memories. Here, we show that the Locus Coeruleus (LC) cells projecting to dCA1 have a key permissive role in contextual memory linking, without affecting contextual memory formation, and that this effect is mediated by dopamine and not by noradrenaline. Additionally, we found that LC to dCA1 projecting neurons modulate the excitability of dCA1 neurons, and the extent of overlap between dCA1 memory ensembles, as well as the stability of coactivity patterns within these ensembles. This discovery of a neuromodulatory system that specifically affects memory linking without affecting memory formation, reveals a fundamental separation between the brain mechanisms that modulate these two distinct processes.

neuroscience↗

bioRxiv2020

Local microcircuitry of parasubiculum shows distinct and common features of excitatory and inhibitory connectivity

The parasubiculum is located within the parahippocampal region, where it is thought to be involved in the processing of spatial navigational information. It contains a number of functionally specialised neuron types including grid cells, head direction cells and border cells, and provides input into layer 2 of the medial entorhinal cortex where grid cells are abundantly located. The local circuitry within the parasubiculum remains so far undefined but may provide clues as to the emergence of spatially tuned firing properties of neurons in this region. We used simultaneous patch-clamp recordings to determine the connectivity rates between the three major groups of neurons found in the parasubiculum. We find high rates of interconnectivity between the pyramidal class and interneurons, as well as features of pyramid to pyramid interactions indicative of a non-random network. The microcircuit that we uncover shares both similarities and divergences to those from other parahippocampal regions also involved in spatial navigation.

neuroscience↗

bioRxiv2018

Challenging the point neuron dogma: FS basket cells as 2-stage nonlinear integrators

Interneurons are critical for the proper functioning of neural circuits and are typically considered to act as linear point neurons. However, exciting new findings reveal complex, sub- and/or supralinear computations in the dendrites of various interneuron types. These findings challenge the point neuron dogma and call for a new theory of interneuron arithmetic. Using detailed, biophysically constrained models, we predict that dendrites of FS basket cells in both the hippocampus and mPFC come in two flavors: supralinear, supporting local sodium spikes within large-volume branches and sublinear, in small-volume branches. Synaptic activation of varying sets of these dendrites leads to somatic firing variability that cannot be explained by the point neuron reduction. Instead, a 2-stage Artificial Neural Network (ANN), with both sub- and supralinear hidden nodes, captures the variance. We propose that FS basket cells have substantially expanded computational capabilities sub-served by their non-linear dendrites and act as a 2-layer ANN.

neuroscience↗