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Berki, P.

Publications and source records attributed to Berki, P..

4 recordsLinked to original sources

Dual thalamic drive defines the intra-amygdala wiring complexity

The amygdala plays a key role in affective behaviors by integrating incoming signals and conveying them towards subcortical output regions. Current models suggest a serial information flow within the amygdala from the lateral and basolateral towards the central subnuclei driven by incoming thalamic and cortical excitation. However, due to the lack of universally accepted parcellation principles, the precise connectivity and thus, the signal propagation within the circuit remain debated. Using a molecular-based parcellation, our subnucleus-specific anatomical and electrophysiological mapping revealed a previously overlooked complexity in the intra-amygdala wiring pattern in mice. Specifically, the intra-amygdala signal transfer relies on separate lateral thalamus-driven routes via the lateral subnucleus mostly bypassing the anterior basolateral and centrolateral subnuclei. In contrast, the anterior basolateral nucleus, innervated by the dorsal midline thalamus, supplies mostly extra-, but not intra-amygdala routes. We also demonstrated that a similar dual thalamo-cortico-amygdala organization exists in the human brain. Collectively, our findings identified unconventional amygdala wiring principles challenging the traditional serial lateral-basolateral-central stream model which can redefine our understanding of behaviorally relevant intra-amygdala computations.

neuroscience↗

A thalamic circuit mechanism for stress-dependent modulation of REM sleep

Rapid eye movement (REM) sleep, a brain state critical for sleep quality and cortical cognition, is tightly controlled by brainstem circuits and highly sensitive to stress. Yet, how these systems interact to regulate REM sleep and its associated forebrain rhythms remains elusive. Here, we identify a thalamic hub that conveys medullary REM-promoting signals, and integrates stress inputs to regulate REM sleep. A subpopulation of paraventricular thalamic neurons that collaterally project to the cortex and nucleus accumbens (PVT[->]NAc) selectively responds to activation of medulla REM-promoting neurons, and bidirectionally modulates REM-associated theta oscillations in an activity-dependent manner. Their low-frequency activation promotes theta rhythms during REM sleep, while high-frequency activation suppresses them, mirroring the neuronal signatures of acute and chronic stress, respectively. Distinct patterns of PVT[->]NAc neurons underlie the bidirectional stress modulation of REM sleep, partly by differentially engaging prefrontal microcircuits via their collateral projections. Together, our findings uncover a thalamic integrative hub that couples sleep-regulating and stress pathways to adaptively control REM sleep expression.

neuroscience↗

Synaptic and dendritic architecture of two types of hippocampal somatostatin interneurons

GABAergic inhibitory neurons fundamentally shape the activity and plasticity of cortical circuits. A major subset of these neurons contains somatostatin (SOM); these cells play crucial roles in neuroplasticity, learning and memory in many brain areas including the hippocampus, and are implicated in several neuropsychiatric diseases and neurodegenerative disorders. Two main types of SOM-containing cells in area CA1 of the hippocampus are oriens-lacunosum-moleculare (OLM) cells and hippocampo-septal (HS) cells. These cell types show many similarities in their soma-dendritic architecture, but they have different axonal targets, display different activity patterns in vivo and are thought to have distinct network functions. However, a complete understanding of the functional roles of these interneurons requires a precise description of their intrinsic computational properties and their synaptic interactions. In the current study we generated, analyzed and make available several key datasets that enable a quantitative comparison of various anatomical and physiological properties of OLM and HS cells in mouse. The dataset includes detailed scanning electron microscopy-based 3-dimensional reconstructions of OLM and HS cells along with their excitatory and inhibitory synaptic inputs. Combining this core dataset with other anatomical data, patch-clamp electrophysiology and compartmental modeling, we examined the precise morphological structure, inputs, outputs, and basic physiological properties of these cells. Our results highlight key differences between OLM and HS cells, particularly regarding the density and distribution of their synaptic inputs and mitochondria. For instance, we estimated that an OLM cell receives about 8400, whereas an HS cell about 15600 synaptic inputs, about 16% of which are GABAergic. Our data and models provide insight into the possible basis of the different functionality of OLM and HS cell types and supply essential information for more detailed functional models of these neurons and the hippocampal network.

neuroscience↗

Rapid microglial phenotype changes modulate neuronal networks and sharp wave-ripple activity in acute slice preparations

Acute brain slices represent a "workhorse" model for studying the central nervous system (CNS) from nanoscale events to complex circuits. While slice preparation inherently involves tissue injury, it is unclear how microglia, the main immune cells and damage sensors of the CNS shape tissue integrity ex vivo. To this end, we have studied the mechanisms of microglial phenotype changes and contribution to neuronal network organisation and functioning in acute brain slices. Using a novel ATP- reporter mouse line and microglia reporter mice, we show that acute slice preparation induces rapid, P2Y12 receptor (P2Y12R) dependent dislocation and migration of microglia, paralleled with marked morphological transformations driven by early ATP surges and subsequent ATP flashes. Gradual depolarization of microglia is associated with the downregulation of purinergic P2Y12R and time-dependent changes of microglia-neuron interactions, paralleled by altered numbers of excitatory and inhibitory synapses. Importantly, functional microglia not only modulate synapse sprouting, but the absence of microglia or microglial P2Y12R markedly diminishes the incidence, amplitude, and frequency of sharp wave-ripple activity in hippocampal slices. Collectively, our data suggest that microglia are inherent modulators of complex neuronal networks, and their specific actions are indispensable to maintain neuronal network integrity and activity ex vivo. These findings could facilitate new lines of research resulting in improved ex vivo methodologies and a better understanding of microglia-neuron interactions both in physiological and pathological conditions.

neuroscience↗