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Kostka, J. K.

Publications and source records attributed to Kostka, J. K..

7 recordsLinked to original sources

Developmental olfactory dysfunction and abnormal odor memory in immune-challenged Disc1+/- mice

Neuronal activity in the olfactory bulb (OB) drives coordinated activity in the hippocampal-prefrontal network during early development. Inhibiting OB output in neonatal mice disrupts functional development of the hippocampal formation as well as cognitive abilities. These impairments manifest early in life and resemble dysfunctions of the hippocampus and the prefrontal cortex that have been linked to neuropsychiatric disorders. Thus, we investigated a disease mouse model and asked whether activity in the OB might be altered, thereby contributing to the dysfunctional development of the hippocampal-prefrontal network. We addressed this question by combining in vivo electrophysiology with behavioral assessment of immune-challenged Disc1+/-mice that mimic the dual genetic-environmental etiology of neuropsychiatric disorders. In wildtype mice, we found high DISC1 expression levels in OB projection neurons during development. Furthermore, neuronal and network activity in the OB, as well as the drive from the bulb to the hippocampal-prefrontal network were reduced in immune-challenged Disc1+/- mice during early development. This early deficit did not affect odor-evoked activity and odor perception but resulted in impaired long-term odor memory. We propose that reduced endogenous activity in the developing OB contributes to altered maturation of the hippocampal-prefrontal network, leading to memory impairment in immune-challenged Disc1+/- mice.

neuroscience↗

Extreme distributions in the preconfigured developing brain

In the adult brain, structural and functional parameters, such as synaptic sizes and neuronal firing rates, follow right-skewed and heavy-tailed distributions. While this organization is thought of having significant implications, its development is still largely unknown. Here, we address this knowledge gap by investigating a large-scale dataset recorded from the prefrontal cortex (PFC) and the olfactory bulb of mice aged 4-60 postnatal days. We show that firing rates and pairwise correlations have a largely stable distribution shape over age, and that neural activity displays a small-world architecture. Moreover, early brain activity displays an oligarchical organization, i.e., neurons with high firing rates are likely to have hub-like properties. Leveraging neural network modeling, we show that analogously extremely distributed synaptic parameters are necessary to recapitulate the experimental data. Thus, functional and structural parameters in the developing brain are already extremely distributed, suggesting that this organization is preconfigured and not experience-dependent.

neuroscience↗

Postnatal development of centrifugal inputs to the olfactory bulb

Processing in primary sensory areas is influenced by centrifugal inputs from higher brain areas, providing information about behavioral state, attention, or context. Activity in the olfactory bulb, the first central processing stage of olfactory information, is dynamically modulated by direct projections from a variety of areas in adult mice. Despite the early onset of olfactory sensation compared to other senses, the development of centrifugal inputs to the olfactory bulb remains largely unknown. Using retrograde tracing across development, we show that centrifugal projections to the olfactory bulb are established during the postnatal period in an area-specific manner. While feedback projections from the piriform cortex are already present shortly after birth, they strongly increase in number during postnatal development with an anterior-posterior gradient. Contralateral projections from the anterior olfactory nucleus are present at birth but only appeared postnatally for the nucleus of the lateral olfactory tract. Numbers of olfactory bulb projecting neurons from the lateral entorhinal cortex, ventral hippocampus, and cortical amygdala show a sudden increase at the beginning of the second postnatal week and a delayed development compared to more anterior areas. These anatomical data suggest that limited top-down influence on odor processing in the olfactory bulb may be present at birth, but strongly increases during postnatal development and is only fully established later in life.

neuroscience↗

Olfactory-driven beta band entrainment of limbic circuitry during neonatal development

Cognitive processing relies on the functional refinement of the limbic circuitry during the first two weeks of life. During this developmental period, when most sensory systems are still immature, the sense of olfaction acts as "door to the world", providing the main source of environmental inputs. However, it is unknown whether early olfactory processing shapes the activity in the limbic circuitry during neonatal development. Here, we address this question by combining simultaneous in vivo recordings from the olfactory bulb (OB), lateral entorhinal cortex (LEC), hippocampus (HP), and prefrontal cortex (PFC) with olfactory stimulation as well as opto- and chemogenetic manipulations of mitral/tufted cells (M/TCs) in the OB of non-anesthetized neonatal mice. We show that the neonatal OB synchronizes the limbic circuity in the beta frequency range. Moreover, it drives neuronal and network activity in LEC, as well as subsequently, HP and PFC via long-range projections from mitral cells (MCs) to HP-projecting LEC neurons. Thus, OB activity shapes the communications within limbic circuits during neonatal development.

neuroscience↗

Bursting mitral cells time the oscillatory coupling between olfactory bulb and entorhinal networks in neonatal mice

Shortly after birth, the olfactory system provides to blind, deaf, non-whisking and motorically-limited rodents not only the main source of environmental inputs, but also the drive boosting the functional entrainment of limbic circuits. However, the cellular substrate of this early communication remains largely unknown. Here we combine in vivo and in vitro patch-clamp and extracellular recordings to reveal the contribution of mitral cell (MC) firing to the early patterns of network activity in the neonatal olfactory bulb (OB) and lateral entorhinal cortex (LEC), the gatekeeper of limbic circuits. We show that MCs predominantly fire either in an irregular bursting or non-bursting pattern during discontinuous theta events in OB. However, the temporal spike-theta phase coupling is stronger for bursting MCs when compared to non-bursting cells. In line with the direct OB projections to LEC, both bursting and non-bursting firing augments during coordinated patterns of entorhinal activity, yet to a higher magnitude for bursting MCs. These cells are stronger temporally coupled to the discontinuous theta events in LEC. Thus, bursting MCs might drive the entrainment of OB-LEC network during neonatal development. KEY POINTSO_LIDuring early postnatal development mitral cells show either irregular bursting or non-bursting firing patterns C_LIO_LIBursting mitral cells preferentially fire during theta bursts in the neonatal OB, being locked to the theta phase C_LIO_LIBursting mitral cells preferentially fire during theta bursts in the neonatal lateral entorhinal cortex and are temporally related to both respiration rhythm- and theta phase C_LIO_LIBursting mitral cells act as cellular substrate of the olfactory drive promoting the oscillatory entrainment of entorhinal networks C_LI

neuroscience↗

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↗

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↗