Biology subjects

Lauri, S.

Publications and source records attributed to Lauri, S..

7 recordsLinked to original sources

bioRxiv2026

Early life stress leads to an aberrant spread of neuronal avalanches in the prefrontal-amygdala network in males but not females

Development of the brain networks is highly vulnerable to stressful events. Early life stress (ELS) has been linked to multifaceted cognitive and emotional deficits in adulthood. Despite a growing body of evidence showing ELS-induced structural and functional changes in the prefrontal cortex (PFC) and basolateral amygdala (BLA), a circuit crucial for emotional processing, our knowledge of the resulting changes in the network dynamics is incomplete. Here, we investigate how maternal separation (MS) affects prefrontal-amygdala network in terms of neuronal avalanches, spatiotemporal clusters of activity, using simultaneous multielectrode recordings in the medial PFC (mPFC) and the BLA of urethane-anaesthetized juvenile (postnatal day (p) 14 - p15) and young adult (p50 - p 60) rats. Firstly, we show that MS leads to an intensified spread of activity within both regions as reflected in the higher mean branching ratios of the avalanches. Next, we demonstrate that most of the avalanches occur locally in one region, however, a small percentage of avalanches has clusters of activity in both regions simultaneously. We show that in MS animals prefrontal clusters followed by activity in the amygdala tend to be larger compared to controls and each event in the mPFC is followed by smaller number of events in the BLA, pointing towards impaired spread of activity from the mPFC to the BLA. Interestingly, avalanche spread from the BLA to the mPFC remains unaffected by MS. Abovementioned effects manifest only in adulthood and, intriguingly, only in males highlighting prolonged developmental and sex-dependent nature of ELS outcome. Significance statementBrain criticality implies that the brain self-organizers towards critical state, characterized by sustained activity propagation reflected in the unitary branching ratios of neuronal avalanches. Here we show how adverse events during early periods of network maturation, namely ELS, can disrupt developmental trajectories of the critical dynamics in the mPFC-BLA circuit in a sex-specific manner. This study broadens our understanding of the critical dynamics emergence in the prefrontal-limbic network and highlights ELS as a potential criticality control parameter.

neuroscience↗

bioRxiv2026

Different developmental trajectories of critical dynamics in prefrontal cortex-amygdala circuitry

Neuronal avalanches, a hallmark of self-organized criticality, represent cascading activity among interconnected neurons. Despite their hypothesized role in neuronal maturation, developmental patterns of neuronal avalanches across interconnected brain regions in vivo remain unelucidated. We applied avalanche analysis to investigate the emergent features of functional connectivity in the developing medial prefrontal cortex-basolateral amygdala (mPFC-BLA) circuitry, using simultaneous electrophysiological recordings from the BLA and mPFC in juvenile and young adult anaesthetized rats. The avalanches were mainly confined to either mPFC or BLA, a small number spanned both regions. Prefrontal avalanches exhibited scale-free behavior with branching ratio close to one and decreasing over development; amygdaloid avalanche size distributions displayed a sharp peak at the maximum size, more pronounced in adulthood, which together with branching ratios over one suggests a deviation from criticality toward a supercritical state. Different dynamical regimes in the BLA and mPFC fit distinct functional demands of these regions.

neuroscience↗

bioRxiv2025

Aberrant development of glutamatergic inputs to PV and SOM interneurons shape amygdala excitability and oscillatory dynamics after early life stress

Early-life stress (ELS) induces persistent amygdala dysfunction and affects amygdala-related emotional behaviors, yet the developmental and physiological mechanisms driving these effects remain poorly understood. Here, we provide a comprehensive electrophysiological characterization of the effects of ELS on parvalbumin and somatostatin interneurons (INs) as well as principal neurons (PNs) in the mouse lateral amygdala (LA) across development. Additionally, we correlate these findings to activity of the LA circuitry in vivo, using Neuropixels recordings in awake mice. In preweaning juveniles, the effects of ELS were remarkably similar in males and females, involving reduced IN excitability, elevated glutamatergic input to INs and shift in the PN E/I balance. While IN function was largely normalized in adult females, males developed a distinct pathological phenotype characterized by reduced glutamatergic input to INs, impaired recruitment of INs and hyperexcitability of PNs. This male-specific dysfunction correlated with aberrant LA oscillatory dynamics in awake mice and deficits in fear processing. Our data suggest that the impaired glutamatergic wiring of interneurons is a key mechanism underlying the aberrant circuit dynamics in the LA after ELS exposure and contribute to the ELS-induced defects in fear processing. These findings highlight sex-specific developmental trajectories of interneuron connectivity as a potential factor contributing to ELS-induced psychiatric vulnerability.

neuroscience↗

bioRxiv2024

GABAB- GluK1 kainate receptor interplay modulates amygdala excitability and behavioral response to chronic stress

Amygdala hyperexcitability is a hallmark for stress-induced anxiety disorders. Stress-associated changes in both principal neurons and interneurons contribute to the increased excitability, but how exactly these mechanisms perturb function of behaviorally relevant circuits in the amygdala remains unclear. Here, we show that GluK1 subunit-containing kainate receptors in parvalbumin (PV) interneurons maintain high GABA release and control excitability of lateral amygdala (LA) principal neurons via tonic GABAB-receptor-mediated inhibition. Downregulation of GluK1 expression in PV interneurons after chronic restraint stress (CRS) releases the tonic inhibition and increases excitability of LA principal neurons. Stress-induced LA hyperexcitability facilitates glutamatergic transmission selectively to central amygdala PKC{delta}-expressing neurons, implicated in fear generalization. Consistent with significance in anxiogenesis, absence of GluK1- GABAB regulation confers resilience against CRS-induced LA hyperexcitability and anxiety-like behavior. Our data reveal a unique novel mechanism involving an interplay between glutamatergic and GABAergic systems in the regulation of amygdala excitability in response to chronic stress.

neuroscience↗

bioRxiv2020

TrkB activation in Parvalbumin interneurons orchestrates cortical plasticity

Activation state of Parvalbumin (PV) interneurons regulates neuronal plasticity, driving the closure of developmental critical periods and alternating between high and low plasticity states in response to experience in adulthood. We now show that PV plasticity states are regulated through the activation of TrkB neurotrophin receptors. Activation of an optically activatable TrkB (optoTrkB) specifically in PV interneurons switches adult cortical networks into a state of elevated plasticity within minutes by decreasing excitability of PV neurons. OptoTrkB activation induces changes in gene expression related to neuronal plasticity and excitability, and increases the phosphorylation of Kv3.1 channels. OptoTrkB activation shifted cortical networks towards a low PV configuration, promoting oscillatory synchrony and ocular dominance plasticity. Visual plasticity induced by fluoxetine was lost in mice lacking TrkB in PV neurons. Our data suggest a novel mechanism that dynamically regulates PV interneurons configuration state and orchestrates cortical networks during adulthood. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=171 SRC="FIGDIR/small/063503v2_ufig1.gif" ALT="Figure 1"> View larger version (54K): org.highwire.dtl.DTLVardef@4c521corg.highwire.dtl.DTLVardef@a2ec04org.highwire.dtl.DTLVardef@353775org.highwire.dtl.DTLVardef@1cc0448_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2019

Antidepressants act by binding to the cholesterol-interaction site at TRKB neurotrophin receptor

It is unclear how binding of antidepressant drugs to their targets gives rise to the clinical antidepressant effect. We discovered that the transmembrane domain of TRKB, the brain-derived neurotrophic factor (BDNF) receptor that promotes neuronal plasticity and antidepressant responses, has a cholesterol-sensing function that mediates synaptic effects of cholesterol. We then found that both typical and fast-acting antidepressants directly bind to TRKB, thereby facilitating synaptic localization of TRKB and its activation by BDNF. Extensive computational approaches including atomistic molecular dynamics simulations revealed a binding site at the transmembrane region of TRKB dimers. Mutation of the TRKB antidepressant-binding motif impaired cellular, behavioral and plasticity-promoting responses to antidepressants in vitro and in vivo. We suggest that binding to TRKB and the allosteric facilitation of BDNF signaling is the common mechanism for antidepressant action, which proposes a framework for how molecular effects of antidepressants are translated into clinical mood recovery.

neuroscience↗

bioRxiv2016

TrkB signaling underlies the rapid antidepressant effects of isoflurane

A brief burst-suppressing isoflurane anesthesia has been shown to rapidly alleviate symptoms of depression in a subset of patients, but the neurobiological basis of these observations remains obscure. We show that a single isoflurane anesthesia produces antidepressant-like behavioural effects in the learned helplessness paradigm and regulates molecular events implicated in the mechanism of action of rapid-acting antidepressant ketamine: activation of brain-derived neurotrophic factor (BDNF) receptor TrkB, facilitation of mammalian target of rapamycin (mTOR) signaling pathway and inhibition of glycogen synthase kinase 3{beta} (GSK3{beta}). Moreover, isoflurane affected neuronal plasticity by facilitating long-term potentiation in the hippocampus. We also found that isoflurane increased activity of the parvalbumin interneurons, and facilitated GABAergic transmission in wild type mice but not in transgenic mice with reduced TrkB expression in parvalbumin interneurons. Our findings strengthen the role of TrkB signaling in the antidepressant responses and encourage further evaluation of isoflurane as a rapid-acting antidepressant devoid of the psychotomimetic effects and abuse potential of ketamine.

neuroscience↗