Synaptic Organization of the Neuronal Circuits of the Claustrum

Abstract

The claustrum, a poorly understood subcortical structure located between the cortex and the striatum, forms widespread connections with almost all cortical areas, but the cellular organization of claustral circuits remains largely unknown. Based primarily on anatomical data, it has been proposed that the claustrum integrates activity across sensory modalities. However, the extent to which the synaptic organization of claustral circuits supports this integration is unclear. Here, we used paired whole-cell recordings and optogenetic approaches in mouse brain slices to determine the cellular organization of the claustrum. We found that unitary synaptic connections among claustrocortical (ClaC) neurons were rare. In contrast, parvalbumin-positive (PV) inhibitory interneurons were highly interconnected with both chemical and electrical synapses. In addition, ClaC neurons and PV interneurons formed frequent synaptic connections. As suggested by anatomical data, we found that corticoclaustral afferents formed monosynaptic connections onto both ClaC neurons and PV interneurons. However, the responses to cortical input were comparatively stronger in PV interneurons. Consistent with this overall circuit organization, activation of corticoclaustral afferents generated monosynaptic excitatory responses as well as disynaptic inhibitory responses in ClaC neurons. These data indicate that recurrent excitatory circuits within the claustrum alone are unlikely to integrate across multiple sensory modalities. Rather, this cellular organization is typical of circuits sensitive to correlated inputs. Although single ClaC neurons may integrate corticoclaustral input from different cortical regions, these results are consistent with more recent proposals implicating the claustrum in detecting sensory novelty or in amplifying correlated cortical inputs to coordinate the activity of functionally related cortical regions.

Anterior Cingulate Cortex Input to the Claustrum Is Required for Top-Down Action Control

“…PV− and PV+ aspiny neurons also exhibited multiple fast inward PSCs beyond E Cl − (Figure S5B). These lines of evidence suggest that the ACC recruits excitatory and inhibitory claustral microcircuits, which elaborates upon previous work (Kim et al, 2016). …”

“…Our data demonstrate that ACC monosynaptically drives claustrum microcircuitry consisting of spiny projection neurons that target cortex, PV− interneurons, and PV+ interneurons. These findings confirm and elaborate upon previous work (Kim et al, 2016). In addition, we found that claustrum amplifies 1- to 10-Hz ACC input persistently but 20-Hz ACC input only transiently and that claustrum inhibitory microcircuits critically constrain this amplification.…”

Frontal cortical control of posterior sensory and association cortices through the claustrum

“…Although claustrum projection neurons are glutamatergic (Brand 1981; Braak and Braak 1982; Hur and Zaborszky 2005; Watakabe et al 2014; Kim et al 2016), the downstream impact of claustrum activity on cortical layers in rodents is unclear. As such, we injected AAV-ChR2 into claustrum (Fig.…”

Mapping synaptic cortico‐claustral connectivity in the mouse

“…Recent electrophysiological observations demonstrate a laminar structure of the claustrum (Orman, ), with the conclusion that the claustrum has strong excitatory connections organized along its rostrocaudal axis, with little connectivity between claustral excitatory neurons along the dorsoventral axis. A recent detailed patch‐clamp study of connectivity in the claustrum in coronal sections of the mouse brain described prevalent inhibitory connectivity of PV neurons onto claustral neurons, and prevalent feed‐forward inhibition driven by cortical inputs to the claustrum (Kim et al, ). Virtually no connections were observed between excitatory claustral neurons in this study, potentially consistent with the observation of Orman (), as these connections were investigated in coronal slices, potentially destroying lateral connectivity in the claustrum.…”