Biology subjects

Grennan, I.

Publications and source records attributed to Grennan, I..

3 recordsLinked to original sources

bioRxiv2025

Modulation of motor cortical theta and gamma oscillations using phase-targeted, closed-loop optogenetic stimulation of local excitatory and inhibitory neurons

Theta and gamma oscillations are prominent features of cortical local field potentials (LFPs) and stimulation of the motor cortex at these frequencies can enhance motor learning. Phase-targeted closed-loop stimulation could provide a more precise and effective method to modulate these oscillations, particularly if stimulation parameters could harness the dynamics of the specific circuit mechanisms underpinning the generation of these activities. To address this question, we defined the response of theta-and gamma-frequency oscillations in the motor cortex to closed-loop optogenetic stimulation of excitatory pyramidal neurons and inhibitory interneurons transfected with Channelrhodopsin-2 in awake, head-fixed RBP4-Cre (retinol-binding-protein-4) and PV-Cre (parvalbumin) mice, respectively. Phase-targeted blue-light pulses were delivered using the OscillTrack algorithm to track theta phase in the cortical LFP in real time and trigger stimulation at one of four target theta phases. Stimulation was delivered over a quarter of the target theta cycle, either as a single continuous pulse ("continuous" protocol) or three short pulses at gamma (75Hz) frequency ("gamma" protocol). Stimulation of both neuron types, using either stimulation protocol, modulated theta power in a phase-dependent manner, with continuous stimulation of excitatory cells leading to stronger modulation. Phase-dependent amplification during stimulation of excitatory vs inhibitory neurons was offset by 90{degrees}, in line with predictions from computational models. Open-loop replay of previously recorded closed-loop stimulation patterns did not elicit the same phase-specific effects, demonstrating the necessity of the closed-loop interaction to produce these effects. Stimulation of pyramidal neurons using the gamma protocol amplified gamma power, independently of target theta phase. These findings reveal phase-dependent amplification of cortical theta power can be induced by stimulation of local excitatory or inhibitory neurons, with a phase-offset likely resulting from circuit interactions. This approach can be used to inform the development of brain stimulation methods to modulate these activities more effectively in humans.

neuroscience↗

bioRxiv2024

Beta bursts in the parkinsonian cortico-basal ganglia network form spatially discrete ensemble.

Defining spatial synchronization of pathological beta oscillations is important, given that many theories linking them to parkinsonian symptoms propose a reduction in the dimensionality of the coding space within and/or across cortico-basal ganglia structures. Such spatial synchronization could arise from a single process, with widespread entrainment of neurons to the same oscillation. Alternatively, the partially segregated structure of cortico-basal ganglia loops could provide a substrate for multiple ensembles that are independently synchronized at beta frequencies. Addressing this question requires an analytical approach that identifies groups of signals with a statistical tendency for beta synchronisation, which is unachievable using standard pairwise measures. Here, we utilized such an approach on multichannel recordings of background unit activity (BUA) in the external globus pallidus (GP) and subthalamic nucleus (STN) in parkinsonian rats. We employed an adapted version of a principle and independent component analysis-based method commonly used to define assemblies of single neurons (i.e., neurons that are synchronized over short timescales). This analysis enabled us to define whether changes in the power of beta oscillations in local ensembles of neurons (i.e., the BUA recorded from single contacts) consistently covaried over time, forming a "beta ensemble". Multiple beta ensembles were often present in single recordings and could span brain structures. Membership of a beta ensemble predicted significantly higher levels of short latency (<5ms) synchrony in the raw BUA signal and phase synchronization with cortical beta oscillations, suggesting that they comprised clusters of neurons that are functionally connected at multiple levels, despite sometimes being non-contiguous in space. Overall, these findings suggest that beta oscillations do not comprise a single synchronization process, but rather multiple independent activities that can bind both spatially contiguous and non-contiguous pools of neurons within and across structures. As previously proposed, such ensembles provide a substrate for beta oscillations to constrain the coding space of cortico-basal ganglia circuits.

neuroscience↗

bioRxiv2023

Hierarchical encoding of reward and effort across the cortex and basal ganglia during cost-benefit decision making

Adaptive value-guided decision-making requires weighing up the costs and benefits of pursuing an available opportunity. Though neurons across frontal cortical-basal ganglia circuits have been repeatedly shown to represent decision-related parameters, it is unclear whether and how this information is coordinated. To address this question, we performed large-scale single unit recordings simultaneously across 5 medial/orbital frontal and basal ganglia regions as rats decided whether to pursue varying reward payoffs available at different effort costs. We found that single neurons encoding combinations of the canonical decision variables (reward, effort and choice) were represented within all recorded brain regions. Co-active cell assemblies - ensembles of neurons that repeatedly co-activated within short time windows (<25ms) within and across structures - were able to provide representations of the same decision variables through the synchronisation of individual neurons with different coding properties. Together, these findings demonstrate a hierarchical encoding structure for cost-benefit computations, where individual neurons with diverse encoding properties are coordinated into larger, low-dimensional spaces within and across brain regions that can signal decision parameters on the millisecond timescale.

neuroscience↗