bioRxiv Science⌕ Search

Biology subjects

Veres, J.

Publications and source records attributed to Veres, J..

4 recordsLinked to original sources

Synaptic communication within the microcircuits of pyramidal neurons and basket cells in the mouse prefrontal cortex

Basket cells are inhibitory interneurons in cortical structures with the potential to efficiently control the activity of their postsynaptic partners. Although their contribution to higher order cognitive functions associated with the medial prefrontal cortex (mPFC) relies on the characteristics of their synaptic connections, the way they are embedded into local circuits is still not fully uncovered. Here, we determined the synaptic properties of excitatory and inhibitory connections between pyramidal neurons (PNs), cholecystokinin-containing basket cells (CCKBCs) and parvalbumin-containing basket cells (PVBCs) in the mouse mPFC. By performing paired recordings, we revealed that PVBCs receive larger unitary excitatory postsynaptic currents from PNs with shorter latency and faster kinetic properties compared to events evoked in CCKBCs. Also, unitary inhibitory postsynaptic currents in PNs were more reliably evoked by PVBCs than by CCKBCs yet the former connections showed profound short-term depression. Moreover, we demonstrated that CCKBCs and PVBCs in the mPFC are mutually interconnected with each other. As alterations in PVBC function have been linked to neurological and psychiatric conditions like Alzheimers disease and schizophrenia and CCKBC vulnerability might play a role in mood disorders, a deeper understanding of the general features of basket cell synapses could serve as a reference point for future investigations with therapeutic objectives.

neuroscience↗

Diversity and connectivity of principal neurons in the lateral and basal nuclei of the mouse amygdala

The basolateral amygdala is a non-layered cortical structure playing a role in various cognitive processes. Despite many studies focusing on local information processing within the circuits of the basolateral amygdala, the characteristics of excitatory principal neurons (PNs) are still not fully revealed. Here, we combined neuroanatomical, electrophysiological, and tracing techniques to determine the single-cell features, dendritic and axonal projections of PNs within the lateral (LA) and basal amygdala (BA). Using a mouse reporter line, we found that cholecystokinin (CCK) expression defines two spatially and functionally segregated groups of PNs both in the LA and BA. PNs in CCK-positive (CCK+) areas of the LA (LAa) had small somata and short dendrites which matched their single-cell electrophysiological properties. PNs in CCK-negative (CCK-) areas of the LA (LAp) and all BA had similarly ramified dendrites and single-cell features with some differences. Importantly, the dendritic arbors of PNs were restricted to the subnuclei defined by CCK expression, which corresponded to various extra-amygdalar afferents indicating specific inputs on distinct PN groups. Axonal arborization patterns of PNs within the basolateral amygdala and surrounding areas showed consistency to their soma location. For instance, BA PNs that projected to the medial prefrontal cortex but not to the lateral nucleus of the central amygdala were present in CCK+ areas. In contrast, those BA PNs that projected to the lateral part of the central nucleus were found in the subnucleus lacking CCK. Our study revealed that the basolateral amygdala is composed of functionally different subnuclei with specific inputs and outputs. This structural arrangement may empower the LA and BA to flexibly channel processed information toward their downstream regions, which can be a key requirement for diverse amygdala functions in cognitive operation.

neuroscience↗

Structural organisation of perisomatic inhibition in the mouse medial prefrontal cortex

Perisomatic inhibition profoundly controls neural function. However, the structural organisation of inhibitory circuits giving rise to the perisomatic inhibition in the higher-order cortices is not completely known. Here, we performed a comprehensive analysis of those GABAergic cells in the medial prefrontal cortex (mPFC) that provide inputs onto the somata and proximal dendrites of pyramidal neurons. Our results show that most GABAergic axonal varicosities contacting the perisomatic region of superficial (layer 2/3) and deep (layer 5) pyramidal cells express parvalbumin (PV) or cannabinoid receptor type 1 (CB1). Further, we found that the ratio of PV/CB1 GABAergic inputs is larger on the somatic membrane surface of pyramidal tract neurons in comparison to those projecting to the contralateral hemisphere. Our morphological analysis of in vitro labelled PV+ basket cells (PVBC) and CCK/CB1+ basket cells (CCKBC) revealed differences in many features. PVBC dendrites and axons arborized preferentially within the layer where their soma was located. In contrast, the axons of CCKBCs expanded throughout layers, though their dendrites were found preferentially either in superficial or deep layers. Finally, using anterograde trans-synaptic tracing we observed that PVBCs are preferentially innervated by thalamic and basal amygdala afferents in layer 5a and 5b, respectively. Thus, our results suggest that PVBCs can control the local circuit operation in a layer-specific manner via their characteristic arborization, while CCKBCs rather provide cross-layer inhibition in the mPFC. Significance StatementInhibitory cells in cortical circuits are crucial for the precise control of local network activity. Nevertheless, in higher-order cortical areas that are involved in cognitive functions like decision making, working memory and cognitive flexibility, the structural organisation of inhibitory cell circuits is not completely understood. In this study we show that perisomatic inhibitory control of excitatory cells in the medial prefrontal cortex is performed by two types of basket cells endowed with different morphological properties that provide inhibitory inputs with distinct layer specificity on cells projecting to disparate areas. Revealing this difference in innervation strategy of the two basket cell types is a key step towards understanding how they fulfil their distinct roles in cortical network operations.

neuroscience↗

Total number and ratio of GABAergic neuron types in the mouse lateral and basal amygdala

GABAergic neurons are key circuit elements in cortical networks. In spite of growing evidence showing that inhibitory cells play a critical role in the lateral (LA) and basal (BA) amygdala functions, neither the number of GABAergic neurons nor the ratio of their distinct types have been determined in these amygdalar nuclei. Using unbiased stereology, we found that the ratio of GABAergic neurons in the BA (22 %) is significantly higher than in the LA (16 %) in both male and female mice. No difference was observed between the right and left hemispheres in either sexes. In addition, we assessed the ratio of the major inhibitory cell types in both amygdalar nuclei. Using transgenic mice and a viral strategy for visualizing inhibitory cells combined with immunocytochemistry, we estimated that the following cell types together compose the vast majority of GABAergic cells in the LA and BA: axo-axonic cells (5.5-6 %), basket cells expressing parvalbumin (17-20 %) or cholecystokinin (7-9 %), dendrite-targeting inhibitory cells expressing somatostatin (10-16 %), NPY-containing neurogliaform cells (14-15 %), VIP and/or calretinin-expressing interneuron-selective interneurons (29-38 %) and GABAergic projection neurons expressing somatostatin and neuronal nitric oxide synthase (nNOS, 5.5-8 %). Our results show that these amygdalar nuclei contain all major GABAergic neuron types as found in other cortical regions. Furthermore, our data offer an essential reference for future studies aiming to reveal changes in GABAergic cell number and in inhibitory cell types typically observed under different pathological conditions, and to model functioning amygdalar networks in health and disease. Significance statementGABAergic cells in cortical structures, like in the lateral and basal nucleus of the amygdala, have a determinant role in controlling circuit operation. In this study, we provide the first estimate for the total number of inhibitory cells in these two amygdalar nuclei. In addition, our study is the first to define the ratio of the major GABAergic cell types present in these cortical networks. Taking into account that hyper-excitability in the amygdala, arising from the imbalance between excitation and inhibition typifies many altered brain functions including anxiety, posttraumatic stress disorder, schizophrenia and autism, uncovering the number and ratio of distinct amygdalar inhibitory cell types offers a solid base for comparing the changes in inhibition in pathological brain states.

neuroscience↗