Research

I seek to understand how cortical circuits contribute to the perception of time.

Cortical Circuits
Cholinergic mechanism for reward timing in primary visual cortex in vivo and in vitro. A) A schematic of the mouse primary visual pathway with the cholinergic nuclei projecting to V1. DB – diagonal band, NBM – nucleus basalis of Meynert, ChAT-ChR2 – Channelrhodopsin-2 expressed under choline acetyltransferase promoter (ChAT). B) Microcircuitry of the visual cortex. Propagation of information through recurrent connections of the network results in persistent neuronal activity. This model system can serve as a test-bed for impairments in functional neuronal connectivity in neurological diseases. C) Response Duration Plasticity (RDP) of persistent activity in V1. i) Representative traces of simultaneous whole-cell patch clamp and extracellular unit recordings. ii) Raster plot of neuronal responses before training. iii) Conditioning by pairing electrical stimulation with a brief pulse of Carbachol (CCh) or blue light (for ChAT-ChR2 transgenic mice) applied at 1s delay. iv) Traces of simultaneous whole-cell and unit recordings post training. v) Raster plot of entrained responses extended to the time of CCh/Light application. vi) Spike-density functions before (black) and post-conditioning (green) represent neuronal responses extended to encode the time of reward (CCh or optogenetic activation of cholinergic fibers expressing Channelrhodopsin-2).
Precise perception of time is an important part of working memory processes that are critical for our cognitive function, including everyday tasks ranging from reading, driving, to solving mathematical problems or playing musical instruments. Persistent neuronal activity has been hypothesized to be the basis of working memory. Thus, temporal dynamics of persistent activity within the neuronal circuit may encode information about time. Although learned temporal relationships are thought to be represented in the frontal and parietal cortices, surprisingly, we have discovered that neurons in rodent primary visual cortex (V1), located at the lowest level of information stream, learn to encode stimulus-reward intervals using modulated patterns of persistent activity. I have developed a visual cortical slice preparation that recapitulates reward timing in vivo. By pairing an electrical stimulus with a cholinergic reward delivered at a fixed temporal delay I can entrain the neuronal network to extend its persistent firing to the time of prospective reward. Reward timing in the primary visual cortex in vivo also requires the cholinergic basal forebrain projections, which provide the reinforcement signal necessary for this learning through a new mechanism of response duration plasticity (RDP).