Lectures and seminars StratNeuro Seminar with Prof. Christopher Moore
Join us for a StratNeuro seminar with Prof. Christopher Moore .
Beyond Neurons: Rapid, Local BBB Permeability Tuned to Behavior and Driven by Dopamine Axons
Choosing correct actions, and learning from them, requires detailed knowledge of current biological needs. Signals carried in vessels are a high-dimensional, unfiltered source of such internal state information for the brain. However, the Forebrain blood-brain barrier (BBB) is typically thought to restrict real-time access to almost all such signals. This constraint is crucial to health, as sustained BBB weakening is a major risk.
A dynamic BBB could resolve this paradox, by providing brief, focal delivery of vascular signals to computing Forebrain circuits, but only when body state information is worth the risk (the ‘State Gate’ Hypothesis). Such events could also provide metabolic microsupply and focal waste clearance, timed and targeted to the focus of activity.
We have found “Plume Events,” transient increases in BBB permeability aligned to key behavioral events. Early in training in a Sensory-cued task, Plume Events occur in two epochs: just before Reward and ~750ms after. Post training, these epochs are again observed, as is a new fast Plume Event response immediately after Sensory Cue. Findings were made in Primary Somatosensory Neocortex using 2-Photon imaging of fluorescent molecule delivery.
We have also found that Dopamine (DA) Axons can drive Plume Events. Optogenetic DA Axon activation drives Plume Events, and endogenous spikes in a subset of these Axons predicts them. Spiking in a different subset predicts preceding Plume Events, suggesting vascular body state information can drive local DA Axon firing, a ‘Hemo-Neural’ effect (Moore and Cao, 2008).
These data support a new conceptual frame and time scale for BBB dynamics, one that is immediate, local and contributes to neural information processing and behavior. I will describe these findings and briefly discuss them in context of our work on other Forebrain meso-scale dynamics related to behavior, such as gamma oscillations (e.g., Siegle*, Pritchett* and Moore, 2014; Shin and Moore, 2019) and DA waves (Hamid, Frank* and Moore*, 2021). I will also briefly discuss new tools we are develop, including using BioLuminescence to drive OptoGenetics (e.g., Optical Synapses Prakash*, Murphy* et al., 2022).