bioRxiv Science⌕ Search

Biology subjects

Hartung, H.

Publications and source records attributed to Hartung, H..

9 recordsLinked to original sources

Genomic Population Structure of Atlantic surfclams: Cryptic Taxonomic Units and Population Connectivity

The Atlantic surfclam, Spisula solidissima solidissima supports multimillion dollar harvests in the western North Atlantic, including Georges Bank and Mid-Atlantic Bight populations along the continental shelf. Surfclam populations in this part of the Exclusive Economic Zone (3-200 nm from shore) are managed as a single unit, but demographic connectivity has never been tested directly. This study analyzed >8,500 SNPs in 548 Atlantic surfclams sampled across the USA harvested range to infer population structure, genomic diversity, and gene flow patterns. Genomic analyses included eight sampled and 10 reference Spisula solidissima similis samples, a morphologically cryptic nominal subspecies previously known only from nearshore habitats. Novel morphologically cryptic population structure was identified in S.s. solidissima. One operational taxonomic unit (OTU-A) was found only in the inshore region of southern New England, south of Cape Cod. The other population unit, OTU-B, was found offshore and in Cape Cod Bay. The federal fishing grounds only had OTU-B clams. Populations within each OTU were connected by gene flow, justifying current fishery management practices. Nearshore state waters had mixed OTU stocks. Hybridization was analyzed between the two OTUs and between the two subspecies based on nuclear SNPs and asymmetrical mitochondrial DNA introgression. Finally, we demonstrated the utility of a novel SNP panel for diagnosing all three taxa and their hybrids.

evolutionary biology↗

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↗

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↗

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↗

Early-life stress impairs development of functional interactions and neuronal activity within prefrontal-amygdala networks in vivo

Early-life stress (ELS), such as parental neglect or abuse, predisposes an individual to develop mental disorders. Disease hallmarks include heightened amygdala reactivity and impaired prefrontal cortex-amygdala functional interactions, already during childhood and adolescence. However, which cellular and circuit mechanisms underlie these hallmarks, as well as the altered developmental trajectory of prefrontal-amygdala networks, is poorly understood. Here we performed simultaneous in vivo local-field potential and multi-unit recordings under light urethane anaesthesia in the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) of male and female pre-juvenile or adolescent mice, exposed to a resource scarcity model of ELS. We find a developmentally transient low-theta (3-5 Hz) oscillatory hypercoupling within mPFC-BLA networks in pre-juvenile ELS males which seems to result from a precocious development of coupling strength after ELS. In the mPFC, neuronal spiking activity was decreased in pre-juvenile males and the local theta entrainment of spike firing disrupted. In BLA, both sexes showed an increase in firing activity in a subpopulation of neurons after ELS, also confirmed by an increase in {Delta}FosB-positive neurons in BLA, which we identified to be non-GABAergic. Directed interactions, i.e. the ability to entrain spike firing in mPFC to the theta rhythm in BLA and vice versa, were also impaired predominantly in pre-juvenile males after ELS, while females showed a milder phenotype. These early sex-dependent impairments in the functional development of prefrontal-amygdala circuits may promote aberrant development of emotional behaviours after ELS and may predispose to a disease phenotype later on.

neuroscience↗

Arginine vasopressin activates serotonergic neurons in the dorsal raphe nucleus during neonatal development in vitro and in vivo

Birth stress is a strong risk factor for psychiatric disorders and associated with an exaggerated release of the stress hormone arginine vasopressin (AVP) into circulation and in the brain. While it has been shown that AVP promotes firing of GABAergic interneurons leading to suppression of spontaneous perinatal hippocampal network events that suggest a protective function, its effect on developing subcortical networks is not known. Here we tested the effect of AVP on the neonatal dorsal raphe nucleus (DRN) 5-hydroxytryptamine (5-HT, serotonin) system, since early 5-HT homeostasis is critical for the development of cortical brain regions and emotional behaviors. Using in vitro electrophysiological recording techniques, we show that AVP strongly excites neonatal 5-HT neurons via V1A receptors by increasing their excitatory synaptic inputs. Accordingly, AVP also promotes action potential firing through a combination of its effect on glutamatergic synaptic transmission and a direct effect on the excitability of 5-HT neurons. Our in vivo single unit recordings of identified neonatal 5-HT neurons under light urethane anaesthesia revealed two major firing patterns of neonatal 5-HT neurons, tonic regular firing and low frequency oscillations of regular spike trains. We confirmed that AVP also increases firing activity of putative 5-HT neurons in neonatal DRN in vivo. Finally, we show that neonatal DRN contains a sparse vasopressinergic innervation that is strongly sex dependent and originates exclusively from vasopressinergic cell groups in medial amygdala and bed nucleus of stria terminalis (BNST). Our results show, that in contrast to developing cortical networks where AVP promotes inhibition, AVP can also be strongly excitatory in immature subcortical networks such as the DRN 5-HT system. Hyperactivation of the neonatal 5-HT system by AVP during birth stress may impact its own ongoing functional development as well as affect maturation of cortical target regions, which may increase the risk for psychiatric conditions later on. Author ContributionsE.O. performed and analysed the in vitro electrophysiological experiments, related immunohistochemistry of filled neurons as well as image analysis, B.K. and H.H. conducted and analysed the in vivo juxtacellular electrophysiological recordings and labelling, related immunohistochemistry of labelled neurons and image analysis, H.H. did the multi-channel in vivo electrophysiological recordings and intracerebral injections as well as related histology, H.T-G. analysed the multi-channel in vivo electrophysiological data, B.K. and H.H. performed the tracing experiments, E.O. and H.H. carried out immunohistochemistry related to the tracing experiments, E.O. performed image analysis related to tracing experiments, M.S. performed and analysed AVP immunocytochemistry experiments in neonatal DRN, H.H. and S.E.L. provided resources for the experimental work and supervised the project. H.H. conceptualized and coordinated the project. The manuscript was written by H.H. with significant contributions from all authors.

neuroscience↗

Transient developmental increase in cortical projections to amygdala GABAergic neurons contribute to circuit dysfunction following early life stress

Early life stress (ELS) results in enduring dysfunction of the cortico-limbic circuitry, underlying emotional and social behavior. However, the neurobiological mechanisms by which ELS affects development of the circuitry remain elusive. Here, we have combined viral tracing and electrophysiological techniques to study the effects of maternal separation (MS) on fronto-limbic connectivity and function in young (P14-21) rats. We report that aberrant prefrontal (mPFC) inputs to basolateral amygdala (BLA) GABAergic interneurons transiently increase the strength of feedforward inhibition in the BLA, which raises LTP induction threshold in MS treated male rats. The enhanced GABAergic activity after MS exposure associates with lower functional synchronization within prefrontal-amygdala networks in vivo. Intriguingly, no differences in these parameters were detected in females, which were also resistant to MS dependent changes in anxiety-like behaviors. Impaired plasticity and synchronization during the sensitive period of circuit refinement may contribute to long-lasting functional changes in the prefrontal-amygdaloid circuitry that predispose to neuropsychiatric conditions later on in life.

neuroscience↗

Coordinated electrical activity in the olfactory bulb gates the oscillatory entrainment of entorhinal networks in neonatal mice

While the developmental principles of sensory and cognitive processing have been extensively investigated, their synergy has been largely neglected. During early life, most sensory systems are still largely immature. As a notable exception, the olfactory system reaches full maturity during intrauterine life, controlling mother-offspring interactions and neonatal survival. Here, we elucidate the structural and functional principles underlying the communication between olfactory bulb (OB) and lateral entorhinal cortex (LEC) - the gatekeeper of limbic circuitry - during neonatal mouse development. Combining optogenetics, pharmacology, and electrophysiology in vivo with axonal tracing, we show that mitral cell-dependent discontinuous theta bursts in OB drive network oscillations and time the firing in LEC via axonal projections confined to upper cortical layers. Pharmacological silencing of OB activity diminishes entorhinal oscillations. Moreover, odor exposure boosts OB-entorhinal coupling at fast frequencies. Thus, early OB activity shapes the maturation of entorhinal circuits.

neuroscience↗

Transient Network Synchrony Of The Developing Medial Entorhinal Cortex

The medial entorhinal cortex (MEC) contains a variety of specialized spatially-tuned neurons whose properties emerge during the third postnatal week onwards in rodents. How neuronal networks underlying the spatial firing patterns are formed is largely unknown but they are hypothesized to develop from topographic modules of synchronized neurons in superficial MEC. Here, we show that developing MEC neuronal networks in the second postnatal week are synchronously active in spatially-grouped modules. Network synchrony is intrinsic to MEC and desynchronized just prior to the emergence of spatially-tuned firing properties. The MEC network is modulated but not driven by the immature hippocampus and is tightly-coupled to neighboring neocortical networks. Unlike hippocampal networks, developing modules are dominated by glutamatergic excitation rather than GABAergic inhibition. Our results demonstrate that intrinsically synchronous modules exist in immature MEC: these may play a key role in establishing and organizing circuitry necessary for spatially-tuned firing properties of MEC neurons.

neuroscience↗