Biology subjects

Argunsah, A. O.

Publications and source records attributed to Argunsah, A. O..

7 recordsLinked to original sources

bioRxiv2026

Adolescent Astrocyte Dysregulation Impairs Prefrontal Interneuron Maturation and Adult Cognition

The prefrontal cortex (PFC), a brain region critical for executive and cognitive functions, is characterized by its protracted maturation extending through adolescence until early adulthood. During adolescence, the PFC undergoes substantial rearrangements, creating a window of heightened plasticity allowing experience-dependent refinement of neural networks. While this extended plasticity supports the development of higher-order cognitive functions, it also confers increased vulnerability to environmental and biological perturbations that can disrupt circuit development and contribute to cognitive and behavioral impairments relevant to psychiatric disorders. Astrocytes are central regulators of brain homeostasis and actively participate in developmental processes that shape postnatal brain maturation. Although astrocyte dysfunction has been increasingly linked to psychiatric pathophysiology, it remains unknown whether aberrant astrocyte activity can directly influence PFC development and cognitive maturation. Here, using selective modulation of astrocyte activity during defined developmental windows in the PFC, we show that abnormal astrocyte activity during adolescence induces transient synaptic loss through enhanced microglial phagocytosis, produces long-lasting alterations in fast-spiking parvalbumin (PV) interneurons, and results in persistent deficits in PFC-dependent behaviors. Together, these findings provide causal evidence that disrupted astrocyte function during adolescent PFC maturation can lead to persistent neuronal and cognitive deficits with relevance to major psychiatric disorders.

neuroscience↗

bioRxiv2025

Learning reorganizes dendritic and stabilizes axonal initial segment inhibitory synapses in CA1 pyramidal neurons

Structural synaptic plasticity underlies the changes in brain connectivity required for learning and memory. Inhibitory synapses (INS) target all subcellular domains of excitatory pyramidal neurons (PNs), including dendrites, somata and axon initial segments (AIS). These subcellular domains have distinct molecular, structural and physiological profiles which underlie their functions. How structural plasticity of INS supports these functions as well as emerging properties such as memory is largely unknown. To tackle these questions we tracked INS on dendrites, somata and AIS of PNs in the dorsal hippocampal CA1 area of mice over two weeks. Size and temporal dynamics of INS showed a strong compartmentalization and dendritic INS were less dynamic than dendritic spines. Trace fear conditioning led to reorganization of dendritic INS and to stabilization of AIS INS but had a minimal effect on dendritic spines. Finally, mathematical modelling allowed us to probe the mechanisms underlying stabilization of INS upon learning.

neuroscience↗

bioRxiv2024

Progressive engagement of SST+ interneurons via Elfn1 regulates the barrel-septa response identity in the somatosensory cortex of mice

Just as separated digits and repeated sampling enhance somatosensation in humans, mice sense objects through multiple segregated whiskers through successive contacts. Individual whisker identity is maintained through the somatotopic organization of the Whisker[->]Brainstem[->]Thalamus[->]Cortex axis, culminating in distinct cortical domains: barrels and the surrounding septa. By performing simultaneous recordings using in-vivo electrophysiology in wild-type (WT) mice, we identify a progressive divergence in spiking activity between these domains upon repeated behaviorally relevant (10Hz) single- and multi-whisker stimulation. While the spiking activity ratio of multi- to single-whisker stimulation remains stable in barrels, it increases progressively in septa, suggesting inhibitory cell recruitment. Using genetic fate-mapping and tissue clearing, we indeed reveal that SST+ and VIP+ interneurons exhibit distinct laminar and regional distributions in barrel and septa domains. Further, calcium imaging of SST+ and VIP+ interneurons shows that while both neuron types respond to single-whisker stimulus, SST+ interneurons preferentially engage more in 10Hz multi-whisker stimulation, indicating their critical role in progressive stimulus preference. Genetic removal of Elfn1, which regulates the incoming excitatory synaptic dynamics onto SST+ interneurons, leads to the loss of the progressive increase in septal spiking ratio (MWS/SWS) upon stimulation. The importance of the loss of functional segregation of barrels, versus septa is revealed by cumulative temporal decoding analysis, supporting the notion that SST+ interneuron-mediated inhibition contributes to temporal encoding and stimulus integration. Finally, viral tracing combined with whole brain clearing and imaging reveals that barrel and septa domains project differentially to secondary somatosensory (S2) and motor (M1) cortices. These distinct projection patterns suggest that differential inhibitory processing in barrels and septa may contribute to functionally specialized downstream signaling. Together, our findings indicate that the progressive engagement of SST+ interneurons, mediated by Elfn1-dependent synaptic facilitation, underlies the preferential integration of multi-whisker stimuli in septa. This local inhibitory mechanism likely contributes to the functional segregation of barrel and septa domains and their distinct cortical projections, shaping how sensory information is processed and relayed to higher-order brain regions.

neuroscience↗

bioRxiv2021

Temporal Pattern of Synaptic Activation Determines the Longevity of Structural Plasticity at Single Dendritic Spines

Individual synapses are the points at which information is passed between neurons, yet it is unknown how the diverse patterns of activity that are observed in vivo effect plasticity at the level of single inputs. Here, we aimed to determine what are the structural plasticity consequences of naturalistic patterns of activity at single spines, as these reflect changes in synaptic efficacy. Utilizing two- photon fluorescence imaging and glutamate uncaging, we studied structural plasticity of individual CA1 hippocampal dendritic spines using activation patterns sampled from a Poisson distribution, which resemble endogenous firing patterns from their CA3 inputs. We found that while the majority of inputs initially undergo structural changes, the robustness of this plasticity is determined by the timing structure of the Poisson sampled naturalistic stimulation patterns. Further, we found that structural plasticity elicited by these naturalistic patterns is both NMDAR and protein synthesis dependent, consistent with requirements for other forms of plasticity. Lastly, we found that during the delivery of naturalistic activity patterns, spines underwent rapid and dynamic structural growth that predicted the longevity of plasticity, which was not the case during non-naturalistic stimulation protocols. These data suggest that dendritic spines are able to integrate incoming temporal information and accordingly modulate the longevity of plasticity that is induced. HighlightsO_LINaturalistic stimulation of single dendritic spines of CA1 hippocampal neurons induces long lasting structural plasticity that depends on the temporal distribution of the synaptic events. C_LIO_LIStructural plasticity induced by naturalistic stimulation patterns requires NMDA receptor activation and new protein-synthesis. C_LIO_LIRapid spine structural dynamics during naturalistic activity, but not regular patterns, predict the longevity of subsequent structural plasticity. C_LI

neuroscience↗

bioRxiv2020

SpineS: An interactive time-series analysis software for dendritic spines

Live fluorescence imaging has shown the dynamic nature of dendritic spines, with changes in shape occurring both during development and in response to activity. The structure of a dendritic spine positively correlates with its functional efficacy. Learning and memory studies have shown that great deal of the information stored by a neuron is contained in the synapses. High precision tracking of synaptic structures can give hints about the dynamic nature of memory and help us to understand how memories evolve both in biological and artificial neural networks. Experiments that aim to investigate the dynamics behind the structural changes of dendritic spines require the collection and analysis of large time-series datasets. In this paper, we present an open-source software called SpineS for the automatic longitudinal structural analysis of dendritic spines with additional features for manual intervention to ensure optimal analysis. Our extensive experimental analyses on multiple datasets demonstrate that SpineS can achieve a high-level performance on samples collected both by two-photon and confocal imaging systems.

neuroscience↗

bioRxiv2020

Post-mitotic Prox1 expression controls the final specification of cortical VIP interneuron subtypes

Neuronal identity is controlled in multiple developmental steps by key transcription factors that determine the unique properties of a cell. During embryogenesis, the transcription factor Prox1 has been shown to regulate VIP interneuron migration, survival, and as a result, circuit integration. Here, we explore the role of Prox1 as a regulator of genetic programs that guide the final specification of VIP interneuron subtypes in early post-natal life. Using in-vitro electrophysiology we find that post-natal removal of Prox1 differentially affects the synaptic integration of VIP bipolar and multipolar subtypes. RNA sequencing reveals that one of the downstream targets of Prox1 is the postsynaptic protein Elfn1, a constitutive regulator of presynaptic release probability. Genetic, pharmacological and electrophysiological experiments demonstrate that knocking out Prox1 reduces Elfn1 function in VIP multipolar but not in bipolar cells. Thus, in addition to the activity-dependent and contextual processes that finalize developmental trajectories, genetic programs engaged by Prox1 control the differentiation and connectivity of VIP interneuron subtypes.

neuroscience↗

bioRxiv2020

Developmental Divergence of Sensory Stimulus Representation in Cortical Interneurons

Two inhibitory cell types involved in modulating barrel cortex activity and perception during active whisking in adult mice, are the VIP+ and SST+ interneurons. Here we identify a developmental transition point of structural and functional rearrangements onto these interneuron types around the start of active sensation at P14. Using in vivo two-photon Ca2+ imaging, we find that before P14, both interneuron types respond stronger to a multi-whisker stimulus, whereas after P14 their responses diverge, with VIP+ cells losing their multi-whisker preference and SST+ neurons enhancing theirs. Rabies virus tracings followed by tissue clearing, as well as photostimulation-coupled electrophysiology reveal that SST+ cells receive higher cross-barrel inputs compared to VIP+ at both time points. In addition, we also uncover that whereas prior to P14 both cell types receive direct input from the sensory thalamus, after P14 VIP+ cells show reduced inputs and SST+ cells largely shift to motor-related thalamic nuclei.

neuroscience↗