Biology subjects

Nguyen, Q.-A.

Publications and source records attributed to Nguyen, Q.-A..

3 recordsLinked to original sources

bioRxiv2025

Distinct Electrophysiological Signatures Define Neuronal Subtypes in the Fasciola Cinereum

The fasciola cinereum (FC) is a small, conserved hippocampal subregion whose cellular properties remain poorly understood. Anatomically positioned between dorsal CA1 and the third ventricle, the FC receives diverse cortical and subcortical inputs but is often excluded from hippocampal circuit models. Here, we performed ex vivo whole-cell patch-clamp recordings in mouse hippocampal slices to define the intrinsic and synaptic properties of FC neurons. We find that FC neurons are electrophysiologically and morphologically distinct from neighboring CA1 and CA2 pyramidal cells, exhibiting reduced intrinsic excitability, delayed spike initiation, and enhanced afterhyperpolarizations. These properties are strongly shaped by potassium conductances, with Kv2 (KCNB) and Kv7 (KCNQ) channels contributing to the suppression of firing. We find that FC neurons span a continuum of intrinsic excitability which is structured by variability in potassium channel-mediated conductances and is inversely coordinated with excitatory synaptic input, such that less excitable neurons receive stronger synaptic drive. Together, these findings establish a mechanistic framework in which intrinsic membrane properties and synaptic input are co-organized across the FC population, providing new insight into how this understudied hippocampal region may contribute to the regulation of neural excitability. Key PointsO_LIThe fasciola cinereum (FC) is a small and poorly understood hippocampal subregion that has recently been implicated in hippocampal related function and seizure activity. C_LIO_LIHere we show that neurons in the FC are morphologically and functionally distinct from cells in neighboring CA1 and CA2 hippocampal subregions, and find substantial physiological diversity of FC neurons, including differences in firing behavior, membrane properties, and intrinsic excitability. C_LIO_LIPharmacological analyses show that Kv2 and Kv7 potassium channels play a key role in shaping the intrinsic properties of FC neurons. C_LIO_LILess excitable FC neurons receive stronger excitatory synaptic input, revealing an inverse relationship between intrinsic membrane excitability and synaptic drive. C_LIO_LIThese findings identify the FC as a physiologically specialized hippocampal subregion and provide a foundation for understanding its role in hippocampal function and neurological disease. C_LI

neuroscience↗

bioRxiv2020

Buildup and bistability in auditory streaming as an evidence accumulation process with saturation

A repeating triplet-sequence ABA_ of non-overlapping brief tones, A and B, is a valued paradigm for studying auditory stream formation and the cocktail party problem. The stimulus is "heard" either as a galloping pattern (integration) or as two interleaved streams (segregation); the initial percept is typically integration then followed by spontaneous alternations between segregation and integration, each being dominant for a few seconds. The probability of segregation grows over seconds, from near-zero to a steady value, defining the buildup function, BUF. Its stationary level increases with the difference in tone frequencies, DF, and the BUF rises faster. Percept durations have DF -dependent means and are gamma-like distributed. Behavioral and computational studies usually characterize triplet streaming either during alternations or during buildup. Here, our experimental design and modeling encompass both. We propose a pseudo-neuromechanistic model that incorporates spiking activity in primary auditory cortex, A1, as input and resolves perception along two network-layers downstream of A1. Our model is straightforward and intuitive. It describes the noisy accumulation of evidence against the current percept which generates switches when reaching a threshold. Accumulation can saturate either above or below threshold; if below, the switching dynamics resemble noise-induced transitions from an attractor state. Our model accounts quantitatively for three key features of data: the BUFs, mean durations, and normalized dominance duration distributions, at various DF values. It describes perceptual alternations without competition per se, and underscores that treating triplets in the sequence independently and averaging across trials, as implemented in earlier widely cited studies, is inadequate. Author summarySegregation of auditory objects (auditory streaming) is widely studied using ambiguous stimuli. A sequence of repeating triplets ABA_ of non-overlapping brief pure tones, A and B, frequency-separated, is a valued stimulus. Studies typically focus on one of two behavioral phases: the early (say, ten seconds) buildup of segregation from the default integration or later spontaneous alternations (bistability) between seconds-long integration and segregation percepts. Our experiments and modeling encompass both. Our novel, data-driven, evidence-accumulation model accounts for key features of the observations, taking as input recorded spiking activity from primary auditory cortex (as opposed to most existing, more abstract, models). Our results underscore that assessing individual triplets independently and averaging across trials, as in some earlier studies, is inadequate (lacking neuronal-accountability for percept duration statistics, the underlying basis of buildup). Further, we identify fresh parallels between evidence accumulation and competition as potential dynamic processes for choice in the brain.

neuroscience↗

bioRxiv2017

A systems approach to the characterization and classification of T-cell responses

Types of T-cell responses are categorized on the basis of a limited number of molecular markers selected using a priori knowledge about T-cell immunobiology. We sought to develop a novel systems-based approach for the creation of an unbiased framework enabling assessment of antigenic-peptide specific T-cell responses in vitro. A meta-analysis of transcriptome data from PBMCs stimulated with a wide range of peptides identified patterns of gene regulation that provided an unbiased classification of types of antigen-specific responses. Further analysis yielded new insight about the molecular processes engaged following antigenic stimulation. This led for instance to the identification of transcription factors not previously studied in the context of T-cell differentiation. Taken together this profiling approach can serve as a basis for the unbiased characterization of antigen-specific responses and as a foundation for the development of novel systems-based immune profiling assays.

genomics↗