Past events

Functional MRI (fMRI) studies have defined a series of visual processing regions in the human cortex, which are believed to enable visual recognition behaviors through a hierarchy of processing stages. At the higher stages in this hierarchy lie regions which preferentially respond to images of intact objects compared to other visual stimuli, a set of regions collectively termed object-selective cortex. Within object-selective cortex exist category-selective regions, which prefer particular categories of images over others (e.g., faces, body parts, houses or scenes). Initially these regions were considered non-retinotopic, but increasing evidence indicates substantial retinal position selectivity, and in some cases retinotopy, in these regions. What is the representation of the visual field in object-selective regions? Are separate object- and category-selective regions part of a single map or embedded within a set of distinct visual field maps? We scanned seven subjects on separate experiments to localize object/category-selective regions, and measure visual field maps (GE 3T scanner). For retinotopic experiments, subjects viewed moving bar stimuli containing different stimuli, including slowly drifting checkerboards and frontal face images. The bars extended out to around 14° eccentricity from the fovea, and had a width of ~2.6°. We employed a recently-developed method for estimating population receptive fields (pRFs) using fMRI (Dumoulin and Wandell, Neuroimage, 2008), which estimates pRF center and size for each cortical location. Face-containing bars produced substantially larger responses than checkerboards along the fusiform gyrus, improving our ability to measure visual field maps in these regions. Eccentricity maps revealed two foveal representations, which may correspond to visual field map clusters previously identified as VO and VT (Wandell et al., Neuro-opth. Jpn., 2006). These foveas are within or adjacent to fusiform face-selective regions, and separated by smoothly-varying extra-foveal maps which are less face-selective. For several subjects, pRF sizes systematically increased with eccentricity in face-selective regions. The distribution of pRF sizes were substantially larger than in earlier visual cortex, but comparable to recent measurements made in lateral occipital cortex. We find two spatially separate face-selective regions along the fusiform gyrus, with comparable visual field coverage, separated by a representation of intermediate eccentricities. This indicates these two regions are likely to fall within different visual field maps. Current work addresses possible effects of low-level visual features (e.g. spatial frequency) and stimulus visibility in driving the observed face-selective retinotopic responses. I will also present some preliminary data from retinotopic mapping with house-containing bars, and an examination of retinotopic organization in house- or scene-selective cortical regions.

Optogenetics, synthesizing microbial opsins and solid-state optics, has achieved the goal of millisecond-precision bidirectional control of defined cell types in freely behaving mammals, but has not yet been widely applied to neuroscience and neuropsychiatry experimental challenges. First, relevant to important basic science questions, we have now successfully developed methods to target and control several classes of modulatory neurons in behaving mammals and intact neural tissue, and we are probing and quantifying measures of altered circuit performance under optogenetic control of defined circuit elements to address longstanding questions about neural circuit dynamics. Second, relevant to neuropsychiatric disease questions, we have used this approach for depth targeting of hypothalamic cells (in this case, the hypocretin/orexin cells in the lateral hypothalamus), establishing for the first time a causal relationship between frequency-dependent activity of genetically defined neurons important in clinical neuropsychiatric disease and a complex orchestrated mammalian behavior. We also are now applying fast optical control and optical imaging to animal models of depression, Parkinson’s Disease, and altered social behavior relevant to autism. Insights into both normal circuit function and disease mechanisms are beginning to emerge from this multidisciplinary technological approach. Prof. Deisseroth is hosted by the students of the Department of Neurobiology, as a part of the departmental students-invited visiting scientist program.

Dopamine neurons of the VTA, that project to the Nucleus Accumbens, have been involved in the initial rewarding properties of addicting compounds and, more appropriately, in the long-lasting changes observed after chronic drug administration and subsequent withdrawal. Indeed, alcohol, opiates cannabinoids and other substances provoke, upon withdrawal, a drastic and marked reduction of dopaminergic tone. In addition, aversive, non drug-related stimuli also reduce dopaminergic physiological tone. Furthermore, recent human studies reported an attenuated response to methylphenidate in alcoholic subjects and a lower (than controls) dopaminergic tone. These changes are paralleled by a lower number of D2 receptors and suggest a general “impoverishment” of dopamine transmission in the addicted brain. Accordingly, a dopamine deficit correlated with alcohol craving, which was associated with a high relapse risk. Similar results were reported for nicotine withdrawn rats. This hypodopaminergic state could be the target of therapies aimed at restoring the deficient dopamine transmission observed after chronic drug administration in preclinical and clinical investigations.