Biology subjects

Andrasi, T.

Publications and source records attributed to Andrasi, T..

4 recordsLinked to original sources

bioRxiv2025

Optical recordings of unitary synaptic connections reveal high and random local connectivity between CA3 pyramidal cells

The hippocampal CA3 region is thought to play crucial roles in episodic memory functions because of the extensive recurrent connections between CA3 pyramidal cells (CA3PCs). However, different methods provided contradicting observations about the synaptic connectivity between CA3PCs. Therefore, we estimated the connectivity rate between individual CA3PCs using a new approach that is not affected by the confounds of conventional methods. Specifically, we used voltage imaging with the Voltron sensor in acute slices from rats of both sexes to test CA3PC connections by detecting spontaneous spiking and subthreshold responses in anatomically identified neurons. We detected 164 monosynaptic excitatory connections in 3078 tested CA3PC-CA3PC pairs. This 5.3% connectivity rate was much higher than that we observed with the theoretically more sensitive patch clamp method in similar experimental conditions, but it remained below the anatomically observed number of CA3PC-CA3PC contacts. We verified that the imaged excitatory connections were mediated by AMPA receptors. Our results also showed that the recurrent connections did not enrich into preferred connectivity motifs and followed a distribution that was consistent with random connectivity in general. Moreover, voltage imaging revealed CA3PCs with distinct firing properties and somatic locations corresponding to previously established heterogeneity and showed that specific connectivity rules create preferred information routes among these subpopulations. Finally, we showed that there is at least one condition, influencing patch clamp recordings but not voltage imaging, that affects the observable functional connections between CA3PCs. Altogether, our results obtained with a new voltage imaging approach argue for high local connectivity rates between CA3PCs. Significance StatementVoltage imaging offers new opportunities to measure synaptic connectivity between individual identified neurons. We employed the Voltron sensor to measure the monosynaptic connectivity between local CA3 pyramidal cells (CA3PCs) in acute slices from rats. Recurrent CA3PC connections are thought to play crucial roles in storing memory. However, the estimated connectivity rates between CA3PCs differ depending on the methods used. We showed that in spite of having a lower signal-to-noise ratio, voltage imaging results showed a much higher connectivity between CA3PCs than patch clamp recordings. Our results also suggest that the recurrent excitatory connections between CA3PCs are random, with preferred connectivity between and within subpopulations of CA3PCs.

neuroscience↗

bioRxiv2024

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↗

bioRxiv2023

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↗

bioRxiv2022

CaMKIIα promoter-controlled circuit manipulations target both pyramidal cells and inhibitory interneurons in cortical networks

A key assumption in studies of cortical functions is that excitatory principal neurons, but not inhibitory cells express calcium/calmodulin-dependent protein kinase II subunit (CaMKII) resulting in a widespread use of CaMKII promoter-driven protein expression for principal cell manipulation and monitoring their activities. Using neuroanatomical and electrophysiological methods we demonstrate that in addition to pyramidal neurons, multiple types of cortical GABAegic cells are targeted by adeno-associated viral vector (AAV) carrying the CaMKII-Channelrhodopsin 2-mCherry construct. We show that the reporter protein, mCherry can visualize a large fraction of different interneuron types, including parvalbumin (PV), somatostatin (SST), neuronal nitric oxide synthase (nNOS) and neuropeptide Y (NPY)-containing GABAergic cells, which altogether cover around 50% of the whole inhibitory cell population in cortical structures. Importantly, the expression of the excitatory opsin Channelrhodopsin 2 in the interneurons effectively drive spiking of infected GABAergic cells even if the detectability of reporter proteins is ambiguous. Thus, our results challenge the use of CaMKII promoter-driven protein expression as a selective tool in targeting cortical glutamatergic neurons using viral vectors.

neuroscience↗