"Actions of acetylcholine in local circuits of the macaque visual cortex"
Wed, February 20, 2013 • 12:00 PM - 1:00 PM • SEA 4.244 (Library/Auditorium)
Faculty Search Candidate for a Faculty Position in Psychology and/or Neurobiology
Anita Disney, Ph.D.
Department of Neurobiology
The Salk Institute for Biological Sciences
Reception with refreshments at 11:30 a.m.
ABSTRACT: After decades of effort, a great deal is now known about the connectivity within and between neural circuits. The connectivity (or wiring) diagrams that arise from this work have in turn been powerful and pervasive drivers of theory and experiment. However, neuromodulatory processes place strong limits on the explanatory power of wiring diagrams. Viewed in the context of the existence of neuromodulation, wiring diagrams become valuable static pictures of the possible connectivity within a dynamic system, but are insufficient to explain even the spiking patterns between pairs of neurons, let alone the activity within local circuits, or the behavior of a whole animal. To fully understand the dynamic and flexible capabilities of neural circuits, we must understand the neuromodulatory influences to which they are subject. Acetylcholine acts as a neuromodulator in the neocortex of mammals and neuromodulation by acetylcholine is a candidate mechanism for arousal and attention, and has a demonstrated role in cortical plasticity. The work I will present approaches the problem of understanding acetylcholine's action in the neocortex from a number of angles designed to elucidate both the structure and function of the system. I also explore how cholinergic structures and functions vary across cortical model systems. The launching point for much of my work is the observation that acetylcholine is released in cortex by volume transmission; that is from release sites which are largely non-synaptic. This non-specific mode of release implies that selectivity in cholinergic effects upon cortical circuits is largely conferred by selective expression of acetylcholine receptors. To dissect the local circuit effects of acetylcholine acting at cholinergic receptors, I have adopted an integrated strategy that combines quantitative anatomical methods with in vivo physiology and pharmacology. Using these techniques I have shown, for example, that in the primary visual cortex of the macaque, nicotinic acetylcholine receptors are found presynaptically at thalamocortical synapses arriving at spiny neurons in layer 4c and that nicotine acts in this layer to enhance the gain of responses to visual stimuli, in a manner reminiscent of attention. Another implication of volume transmission is that the spatiotemporal profile of extra-synaptic acetylcholine concentration is likely to be an important signaling variable for this neuromodulator. In order to be able to measure the spatiotemporal variation in acetylcholine levels during behavior, I have developed a novel multi-electrode array that measures both local physiology (single unit or field potential) and local chemistry (using enzyme-mediated amperometry). I will discuss previous published data on acetylcholine release in cortex as well as preliminary results obtained with my own novel device in the context of my overall research focus and the current emerging theories of the role neuromodulation in cortical circuits.
Thursday, Feb 21st