Biology subjects

Dobolyi, A.

Publications and source records attributed to Dobolyi, A..

7 recordsLinked to original sources

bioRxiv2026

Functional characterization of the lateral septal calbindin neurons in maternal care

The ventral subdivision of the lateral septum (LSv) is a forebrain region linked to maternal care with a high density of calbindin-containing (Cb+) neurons whose properties, connections and functions remain unknown. In the present study, it was established that the majority of pup-activated neurons are inhibitory Cb+ in the LSv and the density of activated neurons in the LSv is close to that of the medial preoptic area (MPOA), a central brain area in maternal care regulation. Electrophysiological recordings of LSvCb+ and LSvCb- neurons revealed that LSvCb+ neurons exhibited higher membrane resistance, lower spike amplitude and rise slope compared to LSvCb- neurons. The chemogenetic inhibition of LSvCb+ neurons led to reduction in pup-licking behavior without affecting other maternal behavior or eliciting anxiety- or depression-like behavior. To regulate licking behavior, LSvCb+ neurons connect with other maternally involved brain areas. Anterograde and retrograde tract-tracing revealed that two-thirds of the MPOA-projecting LSv neurons are Cb+. A subset of neurons within the posterior intralaminar nucleus (PIL) in the lateral thalamus, a proposed relay nucleus of tactile and auditory information from the pups, express a maternally induced neuropeptide, the parathyroid hormone 2 (PTH2). Their fibers closely apposed Cb+ neurons in the LSv. Using double labeling, we also identified PTH2 receptors on LSvCb+ neurons, which are presumably activated by PTH2 released from nearby terminals. Using electron microscopy, we confirmed synaptic connection between PTH2+ fibers and inhibitory neurons in the LSv. The results provide evidence that Cb+ neurons of the LSv are components of the maternal circuitry. Significance StatementMaternal care depends on pup cues, but many responsible circuit elements remain uncharacterized. We identify inhibitory calbindin-expressing neurons in the ventral subdivision of the lateral septum (LSv) containing a major pup-activated neuronal population with distinctive electrical properties. Their selective inhibition reduced pup-licking without affecting other maternal, anxiety- or depression-like behaviors, suggesting a specific role in caregiving. Detailed circuit tracing data revealed that a significant proportion of LSv calbindin-positive neurons extend their projections to the medial preoptic area, a well-established core maternal regulatory region. We further demonstrate synaptic input from maternally relevant parathyroid hormone 2 (PTH2)-expressing thalamic afferents onto LSv inhibitory neurons, possibly conveying pup stimuli. The data suggest that LSv calbindin neurons are key nodes in maternal circuitry.

neuroscience↗

bioRxiv2025

Postpartum enhancement of spatial learning and cognitive flexibility: an IntelliCage study

The transition to motherhood has been shown to result in significant changes in the structure and function of the brain, with particular emphasis on the enhancement of cognitive abilities that are essential for survival. Specifically, in murine models, spatial learning and cognitive flexibility have been identified as critical components of mothering. These abilities facilitate efficient navigation of the environment, resource acquisition, and responsiveness to offsprings needs. While cognitive enhancements during the postpartum period have been observed in various experimental setups, research using long-term data collection with automated monitoring in home cage setup is completely lacking even though it provides a more reliable approach than other experimental procedures. This study aims to address this knowledge gap by systematically examining spatial learning and cognitive flexibility in female mice during the reproductive stages using IntelliCage, with the objective of offering a more comprehensive understanding of maternal cognitive adaptations. Utilising the IntelliCage system, we observed that female mice in the postpartum phase outperformed pregnant and nulliparous females in place learning, reversal learning, and fixed schedule drinking tasks, demonstrating faster adaptation and superior retention of information. These paradigms mirror real-world challenges faced by mothers, such as navigating resources and balancing caregiving with self-maintenance. The enhanced performance demonstrated by the mothers could be attributed to their heightened motivation and cognitive abilities, potentially influenced by substantial hormonal shifts, which have been known to modify neuroplasticity in critical brain regions. The identification of these improvements in maternal behaviour may offer novel insights into the impact of reproductive experiences on brain function, with implications for maternal health and broader cognitive research.

neuroscience↗

bioRxiv2025

Social Touch Suppresses Aggression via Thalamic Mechanisms

Understanding the neural circuitry underlying aggression is critical for both scientific insight and clinical intervention. Here, we identify the posterior intralaminar thalamic nucleus (PIL) as a key node in an anti-aggressive circuit activated by social touch. Using a rodent model, we demonstrate that deprivation of direct physical contact during social isolation leads to heightened aggression. Chemogenetic and optogenetic manipulations reveal that PIL neurons activated by social touch inhibit aggression via excitatory projections to the medial preoptic area (MPOA) of the hypothalamus. This PIL-to-MPOA pathway is suppressed by input from the ventromedial hypothalamic nucleus (VMH). Our findings establish a novel thalamic-hypothalamic circuit that mediates social touch-induced suppression of aggression, offering potential targets for therapeutic intervention in conditions marked by pathological aggression.

neuroscience↗

bioRxiv2022

Cell-specific expression of key mitochondrial enzymes precludes OXPHOS in astrocytes of the adult human neocortex and hippocampal formation

The astrocyte-to-neuron lactate shuttle hypothesis entails that glycolytically derived pyruvate in astrocytes is converted to lactate instead of being catabolized in mitochondria. The mechanism of this metabolic rewiring is unclear. Here we show that astrocytes of the adult human neocortex and hippocampal formation do not express mitochondrial proteins critical for performing oxidative phosphorylation (OXPHOS) to a detectable degree, including cytochrome c and complex IV. Without OXPHOS, human brain astrocytes are bound to produce lactate to avoid interruption of glycolysis.

neuroscience↗

bioRxiv2022

Anti-glutamatergic effects of three lignan compounds: arctigenin, matairesinol and trachelogenin - An ex vivo study on rat brain slices

Arctigenin is a bioactive dibenzylbutyrolactone-type lignan exhibiting various pharmacological activities. The neuroprotective effects of arctigenin were demonstrated to be mediated via inhibition of AMPA/KA type glutamate receptors in the somatosensory cortex of the rat brain. The aim of this study was to compare the effects of arctigenin with matairesinol and trachelogenin on synaptic activity in ex vivo rat brain slices. Arctigenin, matairesinol and trachelogenin were isolated from Arctium lappa, Centaurea scabiosa and Cirsium arvense, respectively, and applied on brain slices via perfusion medium at the concentration range of 0.5-40 M. The effects of the lignans were examined in the CA1 hippocampus and the somatosensory cortex by recording electrically evoked field potentials. Arctigenin and trachelogenin caused a significant dose-dependent decrease in the amplitude of hippocampal population spikes (POPS) and the slope of excitatory postsynaptic potentials (EPSPs), whereas matairesinol (1 M and 10 M) decreased EPSP slope but had no effect on POPS amplitude. Trachelogenin effect (0.5 M, 10 M, 20 M) was comparable to arctigenin (1 M, 20 M, 40 M) (p > 0.05). In the neocortex, arctigenin (10 M, 20 M) and trachelogenin (10 M) significantly decreased the amplitude of evoked potential early component, while matairesinol (1 M and 10 M) had no significant effect (p>0.05). The results suggest that trachelogenin and arctigenin act via inhibition of AMPA/KA receptors in the brain and trachelogenin has a higher potency than arctigenin. Thus, trachelogenin and arctigenin could serve as lead compounds in the development of alternative neuroprotective drugs.

pharmacology and toxicology↗

bioRxiv2022

Transcriptome profiling of the dorsomedial prefrontal cortex in suicide victims

The default mode network (DMN) plays an outstanding role in psychiatric disorders. Still, gene expressional changes in its major component, the dorsomedial prefrontal cortex (DMPFC), have not been characterized. We used RNA-sequencing in postmortem DMPFC samples to investigate suicide victims compared to control subjects. Most of the data variance (79%) was associated with expression changes between suicide and control samples. 1400 genes differed using log2FC > {+/-} 1 and adjusted p-value < 0.05 criteria between groups. Genes associated with depressive disorder, schizophrenia and impaired cognition were strongly overexpressed in top differentially expressed genes. Gene set enrichment and protein-protein interaction network analysis revealed that pathways related to cytokine receptor signaling were enriched in downregulated while glutamatergic synaptic signaling in upregulated genes in suicide individuals. A validated differentially expressed gene, which is known to be associated with mGluR5, was the N-terminal EF-hand calcium-binding proteins 2 (NECAB2). In situ hybridization histochemistry and immunohistochemistry proved that NECAB2 is expressed in 2 different types of inhibitory neurons located in layers II-IV and VI, respectively. Our results imply extensive gene expressional alterations in the DMPFC related to suicidal behavior. Some of these genes may contribute to the altered mental state and behavior of suicide victims.

neuroscience↗

bioRxiv2022

A thalamo-preoptic pathway promoting social touch

Social touch is an important form of communication, it is still unknown how it is processed. Here, we discovered a functional role for a neuronal pathway projecting from the posterior intralaminar thalamic nucleus (PIL) to the medial preoptic area (MPOA) in controlling social contact. Neurons in the PIL and the MPOA were activated by physical contact between female rodents and also by chemogenetic stimulation of PIL neurons. Chemogenetic stimulation of PIL neurons tagged by social contact experience increased direct physical interactions between familiar female rats without affecting other forms of social behavior. Furthermore, selective stimulation of the PIL-MPOA pathway, and the local activation of PIL terminals within the MPOA, elevated direct social contact between the animals suggesting the role of pathway-specific activated cell assemblies. Neurons projecting from the PIL to the MPOA contain the neuropeptide parathyroid hormone 2 (PTH2). The expression of the peptide was induced by social housing, the presence of PTH2 receptor was identified in MPOA neurons, and local injection of PTH2 increased the firing rate of identified preoptic area GABAergic neurons via the PTH2 receptor suggesting that PTH2 acts as a neurotransmitter in the PIL-MPOA pathway. We also found a homologous PIL to MPOA neuronal pathway in the human brain. Altogether, we discovered a direct thalamo-preoptic pathway, which bypasses the cerebral cortex and controls social touch. This pathway originates in neurons expressing PTH2, a neuropeptide recently shown in fish to respond to the social environment. These observations provide evidence for common evolutionary-conserved PTH2-containing social-touch specific engram circuits.

neuroscience↗