Striatal Local Circuitry: A New Framework for Lateral Inhibition Dennis A. Burke, Horacio G. Rotstein, Veronica A. Alvarez  Neuron  Volume 96, Issue 2, Pages 267-284 (October 2017) DOI: 10.1016/j.neuron.2017.09.019 Copyright © 2017 Terms and Conditions

Figure 1 Diversity of Cell Types of Striatal Interneurons The plot represents the estimated proportions of each subtype of striatal interneuron identified based on their expression of neurotransmitter (inner donut), other molecular markers (middle donut), and electrophysiological properties (outer donut). Abbreviations: ACh, acetylcholine; ChAT, choline-acetyl transferase; TAN, tonically active neurons; TH, tyrosine hydroxlase; CR, calretinin; SOM, somatostatin; NOS, nitric oxide synthase; NPY, neuropeptide Y; LTS, low-threshold spiking; NGF, neurogliaform; 5HT3R, serotonin type-3 receptor; FA, fast adapting; PV, parvalbumin; FS, fast spiking. ∗, SOM/NOS LTS neurons are also tonically active, although not classically referred as TANs. Neuron 2017 96, 267-284DOI: (10.1016/j.neuron.2017.09.019) Copyright © 2017 Terms and Conditions

Figure 2 Axo-axonal Modulation in the Striatum Simple diagram of known axo-axonal presynaptic modulation by dopamine and acetylcholine (ACh) in the striatum. D2, dopamine D2 receptor; M5, M5 muscarinic ACh receptor; M2/4, M2 and M4 muscarinic ACh receptors; nAR, nicotinic ACh receptor. Neuron 2017 96, 267-284DOI: (10.1016/j.neuron.2017.09.019) Copyright © 2017 Terms and Conditions

Figure 3 Main Identified Synaptic Connections between Local Striatal Neurons Schematic showing intrastriatal connectivity between interneurons and projection neurons. Interneurons displayed with molecular markers used to identify cells during experiments. Abbreviations: dSPN, direct pathway projecting medium spiny neuron; iSPN, indirect pathway projecting medium spiny neuron; ChAT, choline-acetyl transferase; TH, tyrosine hydroxlase; SOM, somatostatin; NOS, nitric oxide synthase; NPY, neuropeptide Y; NGF, neurogliaform; 5HT3R, serotonin 3 receptor; PV, parvalbumin; Neuron 2017 96, 267-284DOI: (10.1016/j.neuron.2017.09.019) Copyright © 2017 Terms and Conditions

Figure 4 Proposed Model of Organization of Striatal Functional Units with Lateral Inhibition within and between Units (A) Colored circles represent multiple SPNs from each subclass that are activated together during behavior forming a cluster or ensemble. Each functional unit contains one dSPN cluster and one iSPN cluster. Clusters that are active during execution of behavior A are highlighted and have strong output that enhances behavior A (green arrow) and suppresses competing behavior B (red brake). Lateral inhibition from the active clusters further limits activity of the other silent dSPN and iSPN clusters. (B) Basic connectivity of the lateral inhibition within and between the two functional units described. Note that all clusters receive excitatory inputs as well. For simplicity, all interneurons are not included in this early conceptual model. Neuron 2017 96, 267-284DOI: (10.1016/j.neuron.2017.09.019) Copyright © 2017 Terms and Conditions

Figure 5 Diverse Connectivity Patterns for the Lateral Inhibition Generate Diverse Firing Patterns Left: diagram of the connectivity pattern for the lateral inhibition within and between the two functional units. Right: raster plot output from a conductance-based model of SPNs showing the firing of action potentials in response to identical excitatory inputs for each SPN cluster (green for dSPN and red for iSPN clusters) for each functional unit (top raster for FU1, bottom raster for FU2). (A) No lateral connections between cells. (B) “All-to-all” connections between cells with equal synaptic strengths. (C) “All-to-all” connections between cells with asymmetrical connection strengths (iSPN > dSPN). (D) Proposed organization of lateral inhibition between and within units (“structured”) with equal connection strengths. (E) “Structured” connections between cells with asymmetrical connection strengths (iSPN > dSPN). Neuron 2017 96, 267-284DOI: (10.1016/j.neuron.2017.09.019) Copyright © 2017 Terms and Conditions