Biology subjects

Poepplau, J. A.

Publications and source records attributed to Poepplau, J. A..

7 recordsLinked to original sources

bioRxiv2025

Mapping prefrontal afferents along development

The medial prefrontal cortex (mPFC) acts as a hub for cognitive, emotional, and social processes, integrating neuronal inputs from numerous brain regions. Knowledge on the processes underlying formation and myelination of prefrontal afferents is essential for a comprehensive understanding of the emergence, maturation, and refinement of mPFC-dependent behaviors. However, despite detailed investigation of long-range projections to the mPFC in the adult brain, little is known about their maturation. Here, we use retrograde labeling, light-sheet imaging, and automatic cell segmentation to quantify afferent projections to the mPFC from neonatal to adult age. We show that densities of ipsi- and contralateral prefrontal afferents change along development from a widespread bilateral distribution at neonatal age to a predominantly ipsilateral organization. Furthermore, myelination of interhemispheric prefrontal afferents starts only after the decline of neonatal contralateral projections and is followed by temporally elevated projection densities from limbic brain regions. Overall, these distinct developmental dynamics of prefrontal afferents might have major implications for the maturation of mPFC-dependent functional and behavioral outputs.

neuroscience↗

bioRxiv2025

Developmental embedding of parvalbumin interneurons drives local and crosshemispheric prefrontal gamma synchrony

Gamma oscillations are a pivotal trait of cortical cognitive processing. However, the ability to generate gamma oscillations evolves with age and requires cellular adjustments of the underlying neural networks. In the prefrontal cortex, gamma oscillations emerge relatively late compared to other cortical areas, yet the developmental mechanisms leading to the generation of adult-like gamma oscillations are poorly understood. Here, we combine bilateral in vivo electrophysiology and selective optogenetic manipulations of parvalbumin- (PV+) and somatostatin-positive (SOM+) interneurons in the mouse medial prefrontal cortex along late development to investigate their role for the age-dependent maturation of gamma oscillations. We show that crosshemispheric gamma synchrony strengthens with age, in line with the previously reported increase in local gamma power. Following a similar timeline, the inhibitory effect of PV+ interneurons emerges which start to functionally operate within the classical gamma frequency range from adolescence onwards. In contrast, SOM+ interneurons show no such age-dependent functional integration and display their beta oscillation modulating inhibitory effect across age. These data identify the SOM+ to PV+ interneuron switch as a mechanism of gamma ontogeny and emergence of crosshemispheric synchrony in the developing prefrontal cortex. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=199 HEIGHT=200 SRC="FIGDIR/small/653375v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@1a78b6aorg.highwire.dtl.DTLVardef@b21464org.highwire.dtl.DTLVardef@158bad2org.highwire.dtl.DTLVardef@516706_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2020

Anesthetics uniquely decorrelate hippocampal network activity, alter spine dynamics and affect memory consolidation

General anesthesia is characterized by reversible loss of consciousness accompanied by transient amnesia. Yet, long-term memory impairment is an undesirable side-effect. How different types of general anesthetics (GAs) affect the hippocampus, a brain region central to memory formation and consolidation, is poorly understood. Using extracellular recordings, chronic 2-photon imaging and behavioral analysis, we monitor the effects of isoflurane (Iso), medetomidine/midazolam/fentanyl (MMF), and ketamine/xylazine (Keta/Xyl) on network activity and structural spine dynamics in the hippocampal CA1 area of adult mice. GAs robustly reduced spiking activity, decorrelated cellular ensembles, albeit with distinct activity signatures, and altered spine dynamics. CA1 network activity under all three anesthetics was different to natural sleep. Iso anesthesia most closely resembled unperturbed activity during wakefulness and sleep, and network alterations recovered more readily than with Keta/Xyl and MMF. Correspondingly, memory consolidation was impaired after exposure to Keta/Xyl and MMF, but not Iso. Thus, different anesthetics distinctly alter hippocampal network dynamics, synaptic connectivity, and memory consolidation, with implications for GA strategy appraisal in animal research and clinical settings.

neuroscience↗

bioRxiv2020

Gamma activity accelerates during prefrontal development

Gamma oscillations are a prominent activity pattern in the cerebral cortex. While gamma rhythms have been extensively studied in the adult prefrontal cortex in the context of cognitive (dys)functions, little is known about their development. We addressed this issue by using extracellular recordings and optogenetic stimulations in mice across postnatal development. We show that fast rhythmic activity in the prefrontal cortex becomes prominent during the second postnatal week. While initially at about 15 Hz, fast oscillatory activity progressively accelerates with age and stabilizes within gamma frequency range (30-80 Hz) during the fourth postnatal week. Activation of layer 2/3 pyramidal neurons drives fast oscillations throughout development, yet the acceleration of their frequency follows similar temporal dynamics as the maturation of fast-spiking interneurons. These findings uncover the development of prefrontal gamma activity and provide a framework to examine the origin of abnormal gamma activity in neurodevelopmental disorders.

neuroscience↗

bioRxiv2019

Activity-dependent maturation of prefrontal gamma oscillations sculpts cognitive performance

Disturbed neuronal activity in neuropsychiatric pathologies emerges during development and might cause multifold neuronal dysfunction by interfering with apoptosis, dendritic growth and synapse formation. However, how altered electrical activity early in life impacts neuronal function and behavior of adults is unknown. Here, we address this question by transiently increasing the coordinated activity of layer 2/3 pyramidal neurons in the medial prefrontal cortex of neonatal mice and monitoring long-term functional and behavioral consequences. We show that increased activity during early development causes premature maturation of pyramidal neurons and alters interneuron density. Consequently, reduced inhibitory feedback by fast-spiking interneurons and excitation/inhibition imbalance in prefrontal circuits of young adults result in weaker evoked synchronization in gamma frequency. These structural and functional changes ultimately lead to poorer mnemonic and social abilities. Thus, prefrontal activity during early development actively controls the cognitive performance of adults and might be critical for cognitive symptoms of neuropsychiatric diseases.

neuroscience↗

bioRxiv2018

Identifying neurophysiological features associated with anesthetic state in newborn mice and humans

One Sentence SummaryMachine learning reveals consistent features of anesthetic states assessed by intracranial recordings in newborn mice and multichannel EEG in human neonates and infants.\n\nAbstractMonitoring the hypnotic component of anesthesia during surgeries is critical to prevent intraoperative awareness and reduce adverse side effects. For this purpose, electroencephalographic methods complementing measures of autonomic functions and behavioral responses are in use in clinical practice. However, in human neonates and infants existing methods may be unreliable and the correlation between brain activity and anesthetic depth is still poorly understood. Here, we characterize the effects of different anesthetics on activity of several brain areas in neonatal mice and develop machine learning approaches to identify electrophysiological features predicting inspired or end-tidal anesthetic concentration as a proxy for anesthetic depth. We show that similar features from electroencephalographic recordings can be applied to predict anesthetic concentration in neonatal mice, and human neonates and infants. These results might support a novel strategy to monitor anesthetic depth in human newborns.

neuroscience↗

bioRxiv2018

Microglia inhibition rescues developmental hypofrontality in a mouse model of mental illness

Cognitive deficits, core features of mental illness, largely result from dysfunction of prefrontal-hippocampal networks. This dysfunction emerges already during early development, before a detectable behavioral readout, yet the cellular elements controlling the abnormal maturation are still unknown. Combining in vivo electrophysiology and optogenetics with neuroanatomy and pharmacology in neonatal mice mimicking the dual genetic - environmental etiology of psychiatric disorders, we identified pyramidal neurons in layer II/III of the prefrontal cortex as key elements causing disorganized oscillatory entrainment of local circuits in beta-gamma frequencies. Their abnormal firing rate and timing result from sparser dendritic arborization and lower spine density. Pharmacological modulation of aberrantly hyper-mature microglia rescues morphological, synaptic and functional neuronal deficits and restores the early circuit function. Elucidation of the cellular substrate of developmental miswiring related to later cognitive deficits opens new perspectives for identification of neurobiological targets, amenable to therapies.\n\nHighlightsO_LIMice mimicking the etiology of mental illness have dysregulated prefrontal network\nC_LIO_LIStructural and synaptic deficits cause abnormal rate and timing of pyramidal firing\nC_LIO_LIWeaker activation of prefrontal circuits results from deficits of pyramidal neurons\nC_LIO_LIRescue of microglial function restores developing prefrontal circuits\nC_LI

neuroscience↗