Biology subjects

Petersen, P.

Publications and source records attributed to Petersen, P..

7 recordsLinked to original sources

bioRxiv2025

Argon inhibits autophagy and improves cerebral ischemia-reperfusion injury via PI3K/Akt/mTOR pathway

It has been reported that argon has neuroprotective effects during cerebral ischemia-reperfusion injury (CIRI). However, the specific mechanism is not fully understood. The aim of this study is to investigate if argon could regulate autophagy to exert a neuroprotective function. A temporary middle cerebral artery ischemia mouse model (tMCAO, ischemia 3h, reperfusion 1h) and the HT22 cell line Oxygen glucose deprivation reperfusion (OGDR) model were used for argon treatment. Transcriptome sequencing and bioinformatics analysis were performed on HT22 OGDR models. Western blot, CCK-8, LDH, transmission electron microscopy, agonists and inhibitors of autophagy and PI3K/Akt/mTOR were used to investigate the specific mechanism. Argon could reduce infarct volume, improve weight recovery, and neurological scores. Enrichment analysis of the KEGG signaling pathway was highly correlated with the PI3K/Akt pathway. Western blot, CCK-8, LDH, and transmission electron microscopy showed that argon could activate the PI3K/Akt/mTOR pathway and inhibit autophagy, promoting a neuroprotective function. After the combined use of autophagy inducer 3, Akt inhibitor MK2206, and mTOR inhibitor rapamycin, respectively, the neuroprotective function of argon was significantly reversed. Our study suggests that argon activating the PI3K/Akt/mTOR pathway and inhibiting autophagy is an important mechanism for its neuroprotective function.

neuroscience↗

bioRxiv2025

MITF regulates gene expression in middle tufted neurons and other projection neurons of the olfactory bulb

The microphthalmia-associated transcription factor (MITF) is a master transcription factor in melanocytes and plays equally important roles in mast cells. It is required for the generation, differentiation, and function of these cell types in vertebrates. Mitf is also expressed in the projection neurons of the olfactory bulb (OB), the mitral and tufted (M/T) cells. Loss of Mitf leads to neuronal hyperactivity in primary M/T cells but the general function of Mitf in neurons is unknown. Here, we identify putative MITF target genes in M/T cells, which show limited overlap with known targets in other cell types. These genes can be divided into two groups, those likely to inhibit neuronal activity and genes expressed specifically in a subclass of tufted cells, the middle tufted cells (mTCs). The mTCs are reduced in number in the Mitf mutant OB, suggesting a role for Mitf in the generation or survival of the mTCs and/or their function. Significance statementIdentifying MITF target genes in the OB offers insights into its role in olfaction and the regulation of neuronal activity as well as uncovering its role in mTCs. MITF may play a role in various other processes in neurons.

neuroscience↗

bioRxiv2024

Ex vivo functional characterization of mouse olfactory bulb projection neurons reveals a heterogenous continuum

Mitral and tufted cells in the olfactory bulb (OB) act as an input convergence hub and transmit information to higher olfactory areas. Since first characterized, they have been classed as distinct projection neurons based on size and location: laminarly-arranged mitral cells with a diameter larger than 20{micro}m in the mitral layer (ML), and smaller tufted cells spread across both the ML and external plexiform layer (EPL). Recent in vivo work has shown that these neurons encode complementary olfactory information, akin to parallel channels in other sensory systems. Yet, many ex vivo studies still collapse them into a single class, mitral/tufted, when describing their physiological properties and impact on circuit function. Using immunohistochemistry and whole-cell patch clamp electrophysiology in fixed or acute slices from adult mice, we attempted to align in viv o and ex vivo data and test a soma size-based classifier of OB projection neurons using passive and intrinsic firing properties. We found that there is no clear separation between cell types based on passive or active properties. Rather, there is a heterogeneous continuum with three loosely clustered subgroups: EPL tufted cells, and putative tufted or putative mitral cells in the ML. These findings illustrate the large functional heterogeneity present within the OB projection neurons and complement existing literature highlighting how heterogeneity in sensory systems is preponderant and possibly used in the OB to decode complex olfactory information.

neuroscience↗

bioRxiv2024

Reduction in olfactory ability in aging Mitf mutant mice without neurodegeneration

Age-related decline occurs in most brain structures and sensory systems. An illustrative case is olfaction, where the olfactory bulb (OB) undergoes deterioration with age, resulting in reduced olfactory ability. Decline in olfaction is also associated with early symptoms of neurodegenerative diseases including Alzheimers disease (AD) and Parkinsons disease (PD). However, the underlying reasons are unclear. The microphthalmia-associated transcription factor (MITF) is expressed in the projection neurons (PNs) of the OB - the mitral and tufted (M/T) cells. Primary M/T cells from Mitf mutant mice show hyperactivity, potentially attributed to reduced expression of a key potassium channel subunit, Kcnd3/Kv4.3. This influences intrinsic plasticity, an essential mechanism involving the non-synaptic regulation of neuronal activity. As neuronal hyperactivity often precedes neurodegenerative conditions, the current study aimed to determine whether the absence of Mitf has degenerative effects during aging. Aged Mitf mutant mice showed reduced olfactory ability without inflammation. However, an increase in the expression of potassium channel subunit genes in the OB suggests that during aging compensatory mechanisms lead to stabilization. Significance statementThis study highlights the age-related decline in olfaction and elucidates compensatory mechanisms mediated by potassium channels. These findings improve our comprehension of the processes underlying age-related changes in olfaction.

neuroscience↗

bioRxiv2021

Movement is governed by rotational population dynamics in spinal motor networks

Although the generation of movements is a fundamental function of the nervous system, the underlying neural principles remain unclear. Since flexor- and extensor-muscles alternate during rhythmic movements like walking, it is often assumed that the responsible neural circuitry is similarly displaying alternating activity. Here, we present ensemble-recordings of neurons in the lumbar spinal cord that indicate that, rather than alternating, the population is performing a low-dimensional "rotation" in neural space, in which the neural activity is cycling through all phases continuously during the rhythmic behavior. The radius of rotation correlates with the intended muscle force and a perturbation of the low-dimensional trajectory can modify the motor behavior. Since existing models of spinal motor control offer an inadequate explanation of rotation, we propose a new theory of neural generation of movements from which this and other unresolved issues, such as speed regulation, force control, and multi-functionalism, are readily explained.

neuroscience↗

bioRxiv2020

Metal microdrive and head cap system for silicon probe recovery in freely moving rodent

High-yield electrophysiological extracellular recording in freely moving rodents provides a unique window into the temporal dynamics of neural circuits. Recording from unrestrained animals is critical to investigate brain activity during natural behaviors. The use and implantation of high-channel-count silicon probes represent the largest cost and experimental complexity associated with such recordings making a recoverable and reusable system desirable. To address this, we have designed and tested a novel 3D printed head-gear system for freely moving mice and rats. The system consists of a recoverable microdrive printed in stainless steel and a plastic head cap system, allowing researchers to reuse the silicon probes with ease, decreasing the effective cost, and the experimental effort and complexity. The cap designs are modular and provide structural protection and electrical shielding to the implanted hardware and electronics. We provide detailed procedural instructions allowing researchers to adapt and flexibly modify the head-gear system.

neuroscience↗

bioRxiv2018

Mitf links neuronal activity and long-term homeostatic intrinsic plasticity

Neuroplasticity forms the basis for neuronal circuit complexity and can determine differences between otherwise similar circuits. Although synaptic plasticity is fairly well characterized, much less is known about the molecular mechanisms underlying intrinsic plasticity, especially its transcriptional regulation. We show that the Microphthalmia-associated transcription factor (Mitf), best known as the master regulator of melanocytic cell fate and differentiation, plays a central role in homeostatic intrinsic plasticity of olfactory bulb (OB) projection neurons. Mitral and tufted (M/T) neurons from Mitf mutant mice are hyperexcitable due to reduced Type-A potassium current (IA) and they exhibit reduced expression of Kcnd3, which encodes a potassium voltage-gated channel subunit (Kv4.3) important for generating the IA. Furthermore, expression of the Mitf and Kcnd3 genes is activity-dependent in OB projection neurons, The MITF protein binds to and activates expression from Kcnd3 regulatory elements. Activity can therefore affect Kcnd3 expression directly via MITF. Moreover, Mitf mutant mice have changes in olfactory habituation and have increased habitutation for an odourant following long-term exposure, indicating that regulation of Kcnd3 is pivotal for long-term olfactory adaptation. Our findings show that Mitf acts as a direct regulator of intrinsic homeostatic feedback, plays a key role in olfactory adaptation and links neuronal activity, transcriptional changes and neuronal function. Significance statementA direct, Mitf-dependent link between neuronal activity and homeostatic changes in the expression of a key potassium channel subunit is demonstrated in projection neurons of the mouse OB. This is one of the first studies that directly link activity and genetically defined changes in intrinsic plasticity, leading to changes in neuronal response. These findings broaden the general understanding of transcriptional regulation of homeostatic intrinsic plasticity in learning and memory. The results are also important for understanding the role of Mitf in other cell types. Regulation of intrinsic plasticity has wide-ranging implications and fundamental importance for neurological diseases such as neurodegeneration, autism and epilepsy.

neuroscience↗