Abstract
Quantitative analysis of corticocortical signaling is needed to understand and model information processing in cerebral networks. However, higher-order pathways, hodologically remote from sensory input, are not amenable to spatiotemporally precise activation by sensory stimuli. Here, we combined parametric channelrhodopsin-2 (ChR2) photostimulation with multi-unit electrophysiology to study corticocortical driving in a parietofrontal pathway from retrosplenial cortex (RSC) to posterior secondary motor cortex (M2) in mice in vivo. Ketamine anesthesia was used both to eliminate complex activity associated with the awake state and to enable stable recordings of responses over a wide range of stimulus parameters. Photostimulation of ChR2-expressing neurons in RSC, the upstream area, produced local activity that decayed quickly. This activity in turn drove downstream activity in M2 that arrived rapidly (5–10 ms latencies), and scaled in amplitude across a wide range of stimulus parameters as an approximately constant fraction (~0.1) of the upstream activity. A model-based analysis could explain the corticocortically driven activity with exponentially decaying kernels (~20 ms time constant) and small delay. Reverse (antidromic) driving was similarly robust. The results show that corticocortical signaling in this pathway drives downstream activity rapidly and scalably, in a mostly linear manner. These properties, identified in anesthetized mice and represented in a simple model, suggest a robust basis for supporting complex non-linear dynamic activity in corticocortical circuits in the awake state.
Highlights
Corticocortical pathways support inter-areal communication, which is central to behavior (Felleman and Van Essen, 1991; Mišicand Sporns, 2016)
After a recovery period of several weeks, animals were anesthetized with ketamine and underwent placement of a photostimulation fiber over the retrosplenial cortex (RSC) and silicon probes in both the RSC and M2 (Figure 1C). (As described at the end of the Results, a second optical fiber was routinely placed over the M2 to enable antidromic activation; the main focus of the study is on the “forward” orthodromic signaling evoked by RSC stimulation.)
The brief burst of multi-unit activity observed in M2 (Figures 1I-K) arriving shortly after that in RSC (Figures 1E-G) suggests that spiking activity in RSC neurons propagated via their corticocortical axons and synaptically drove spiking activity in M2 neurons, via the abundant excitatory RSC→M2 connections previously described for this corticocortical circuit (Yamawaki et al, 2016)
Summary
Corticocortical pathways support inter-areal communication, which is central to behavior (Felleman and Van Essen, 1991; Mišicand Sporns, 2016). Quantitative characterization of signaling in corticocortical pathways is essential for understanding and modeling how they contribute to information-processing. This information can help to address a fundamental question in connectomics research, of how the relatively static structure of corticocortical networks can give. Scaling of Corticocortical Signaling rise to the complex non-linear dynamic activity typically observed in awake animals (Park and Friston, 2013). It is unknown whether such non-linearities are present already at the most basic level of the intrinsic biophysical properties of corticocortical connections, or whether they arise at higher levels of network interactions. Extracellular electrical stimulation has been used in efforts to artificially generate focal activity, but is inherently limited due to its non-specificity, antidromic activation, and other issues (Nowak and Bullier, 1998; Histed et al, 2009)
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