Neuromod+ Early Career Researcher (ECR) award

Steven Errington has been awarded the EPSRC/MRC-funded Neuromod+ Early Career Researcher (ECR) award to present his laminar optogenetic work at the 10th International Workshop on Technologies for Optogenetics and Neurophotonics, Optogen conference in Copenhagen, Denmark.

Laminae specific optogenetic perturbation of frontotemporal circuits in macaques.

Steven P. Errington, Beshoy Agayby, Emma Woolgar, Christopher Morris, Timothy D. Griffiths, Christopher I. Petkov, Yukiko Kikuchi. 

Perceptual inference is a fundamental function in humans and nonhuman animals, allowing the brain to construct meaningful representations of the environment. Predictive coding theories suggest that this process relies on internal models built by cortical microcircuits, the functional units of the neocortex. In these models, superficial layers in sensory cortex are thought to compute prediction errors and relay them to higher-order brain areas such as prefrontal cortex through gamma oscillations, while deeper layers in higher-order areas encode predictions that are feedback to sensory cortex through low-frequency oscillations.  To probe these mechanisms, developing precise circuit-level manipulations with high spatial and temporal resolution is crucial, yet their application in macaque models remains challenging. Here, we present preliminary findings from an awake macaque monkey, demonstrating optogenetic manipulation of single-neurons and local field potentials limited to specific cortical layers. The viral vector AAV9-CamKII-ChR2-eYFP was injected into the rostral part of the non-primary auditory cortex (rAC) and the ventrolateral prefrontal cortex (areas 44/45) to specifically target pyramidal neurons for channelrhodopsin (ChR2) light sensitive ion channel expression, activated by blue light. Single-unit activity and local field potentials (LFPs) were simultaneously recorded from the auditory and frontal cortices with 16-channel linear electrode arrays (Plexon S-probes) integrated with optical fibres. Stimulation with blue- (473 nm) or red- (635 nm) laser light was applied in one-second bursts at either theta (5 Hz) or gamma (40 Hz) frequencies, targeting either superficial or deeper cortical layers. In our preliminary results, we have identified single-units that exhibited modulation in response to optogenetic stimulation in the site of stimulation. These neurons fired action potentials at the same frequency as the applied stimulation and selectively for the blue, but not the red, laser light stimulation wavelength, providing direct evidence of targeted optogenetic activation at cellular resolution. Furthermore, similar wavelength-dependent changes were observed in the LFP power, specific to the frequency of stimulation. By regulating the laser light intensity, we were able to titrate the spatial specificity of these effects to certain sets of layers. Finally, we demonstrated that optogenetic manipulation of neurons in one region resulted in rapid changes in single-unit activity and LFP power within the interconnected region, providing novel neurophysiological evidence for excitatory connections between these two areas. These results highlight the ability to modulate activity with high spatiotemporal precision in single neurons across the cortical layers in a primate model, targeting either superficial or deeper layers of the cortex. This laminar resolution approach enables the dissection of cortical microcircuits, providing insights into fronto-temporal neuronal circuit motifs underlying perceptual inference in the primate brain.  

Supported by MRC & ERC

Last modified: Sun, 30 Mar 2025 15:18:00 BST