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Presentation at SfN 2022, San Diego, CA. Program No. 272.08.

The basal ganglia play an important role in a variety of functions including decision making and action selection mainly based on input from cortex, thalamus and the dopamine system. Striatum is the input stage of the basal ganglia. Here we present a new approach to model the postsynaptic currents mediated by NMDA or AMPA receptors which allows a more accurate description of them. Then we model the extrinsic inputs from cortex and thalamus to the different populations of striatal neurons (striatal projection neurons (dSPNs and iSPNs); cholinergic (ChIN), fast-spiking (FS), and low-threshold spiking (LTS) interneurons). Synapses are critical when investigating microcircuit functions and dynamics, therefore it is necessary to have a computationally efficient and accurate framework to model them. Here we are improving such a pipeline using morphologically detailed neurons. Our method is generic and hence applicable to any brain region. We are working on the integration of these models into large scale networks as part of our ongoing effort to create detailed simulations of the entire striatum.

Figure S1. Flow cytometry and qRT-PCR quality control of cellular samples used for molecular profiling. Figure S2. Differential gene and protein expression analysis and overlap of RNA-Seq and proteomics data. Figure S3. Exploratory analysis of RNA-Seq and proteomics data. Figure S4. Estimated number of proteins per cell based on iTreg proteomics data. Figure S5. Gene Ontology and pathway enrichment analysis of the DEG and DEP clusters. Figure S6. iTreg subnetwork reconstruction strategy. Figure S7. Features of the iTreg candidate molecules and the confirmatory independent RNA-Seq dataset. Figure S8. Linear Discriminant and Random Forest analyses confirm the potential of candidate genes to classify iTregs. Figure S9. Experimental validation of novel FOXP3+ Treg regulatory molecules. (PDF 3722 kb)

The general structure of the mammalian neocortex is remarkably similar across different cortical areas. Despite certain cytoarchitectural specializations and deviations from the general blueprint, the principal organization of the neocortex is relatively uniform. It is not known, however, to what extent stereotypic synaptic pathways resemble each other between cortical areas, and how far they might reflect possible functional uniformity or specialization. Here, we show that frequency-dependent disynaptic inhibition (FDDI) is a generic circuit motif that is present in all neocortical areas we investigated (primary somatosensory, auditory and motor cortex, secondary visual cortex and medial prefrontal cortex of the developing rat). We did find, however, area-specific differences in occurrence and kinetics of FDDI and the short-term dynamics of monosynaptic connections between pyramidal cells (PCs). Connectivity between PCs, both monosynaptic and via FDDI, is higher in primary cortices. The long-term effectiveness of FDDI is likely to be limited by an activity-dependent attenuation of the PC-interneuron synaptic transmission. Our results suggest that the basic construction of neocortical synaptic pathways follows principles that are independent of modality or hierarchical order within the neocortex.

The synchronous oscillatory activity characterizing many neurons in a network is often considered to be a mechanism for representing, binding, conveying, and organizing information. A number of models have been proposed to explain high-frequency oscillations, but the mechanisms that underlie slow oscillations are still unclear. Here, we show by means of analytical solutions and simulations that facilitating excitatory (E(f)) synapses onto interneurons in a neural network play a fundamental role, not only in shaping the frequency of slow oscillations, but also in determining the form of the up and down states observed in electrophysiological measurements. Short time constants and strong E(f) synapse-connectivity were found to induce rapid alternations between up and down states, whereas long time constants and weak E(f) synapse connectivity prolonged the time between up states and increased the up state duration. These results suggest a novel role for facilitating excitatory synapses onto interneurons in controlling the form and frequency of slow oscillations in neuronal circuits.