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.

Traditionally, the brain and sensory cortex in particular have been viewed as being primarily driven by external events, but recent studies in anesthetized animals revealed robust spontaneous activity in sensory cortex, highlighting the intrinsic nature of brain processing. Using fMRI we found widespread slow fluctuations occurring spontaneously in the human visual cortex in the absence of external stimuli. These waves exhibited a consistent and specific neuro-anatomical distribution, suggesting that they largely reflect neuronal activity rather than hemodynamic noise sources. In further studies we obtained neurophysiological recordings in neurosurgical patients, and found direct electrophysiological evidence for such slow spontaneous neuronal fluctuation in human sensory cortex. These fluctuations were evident mainly in neuronal firing rates and in LFP gamma power changes, showed unique temporal dynamics following 1/f power laws, and were found to be correlated between corresponding ‘mirror’ sites across hemispheres within specific functional networks. Overall, these results extend previous animal studies of spontaneous activity by revealing and characterizing such activity in human sensory cortex.

Animal models used to study neuronal mechanisms of drug addiction most commonly rely upon either repeated experimenter-administered cocaine or drug-administration protocols that result in stable patterns of drug-taking. However, it is well established that differences in the route of administration (IV vs. IP or SC) and in the control over administration (self-administered vs. experimenter-administered) lead to differences in cocaine-induced neurochemical effects. In addition, the neural consequences of cocaine administration are different when tested in the middle of the administration protocol, immediately after the last administration of cocaine, or after 2, 14 or 60 days of withdrawal. Finally, the frequency and size of the daily-dose of cocaine are important factors determining the nature of the changes induced by cocaine. It would seem, then, that if we are to better understand the neuroadaptations that underlie the development of addiction in humans, animal models that mimic as closely as possible the human situation should be employed. Hence, my lab uses an animal model that employs an IV route of administration (as opposed to IP or SC), requiring self-administration (as opposed to experimenter-administered), under conditions (based on Ahmed & Koob, 1998) that distinguish the effects of short versus extended daily access to cocaine upon both behavior and neural substrates. This permits the investigation of neuroadaptations associated with the transition from the drug-naïve state to controlled drug-use, versus the further adaptations associated with the transition from controlled to compulsive drug-use. The differences we found, in both behavior and underlying neuronal adaptations, between controlled and compulsive drug-states, will be discussed in this talk.

When a rat runs through a familiar environment, the hippocampus retrieves a previously stored spatial representation of the environment. When the environment is modified a new representation is seen, presumably corresponding to the hippocampus encoding the new information. I will present single unit data on examining the issue of how the “hippocampus decides” whether to retrieve an old representation or form a new representation.

Vibrissal information is relayed to the barrel cortex through at least two parallel pathways: a lemniscal pathway involving the ventroposterior medial thalamic nucleus (VPM), and a paralemniscal pathway involving the posteromedial nucleus (POm). I will review the role of the lemniscal system, focusing on the mechanisms by which VPM shapes the response properties of neurons in cortical barrels. I will argue that although analyses of these properties (e.g. receptive field structure and angular preference) have illuminated the process of input transformation in sensory pathways, they may have only limited ethological role. I will show that this lemniscal pathway is critical for temporal coding of somatosensory inputs. In the paralemniscal pathway, and in POm in particular, neurons respond poorly and unreliably to physiologically relevant stimuli. I will show that the GABAergic nucleus zona incerta (ZI) regulates POm activity is a state-dependent manner. This regulation is mediated by the cholinergic activating system, which enhances POm activity during states of arousal and vigilance. However, even in these states, POm neurons fail to reliably encode sensory inputs. I will show that POm is critically involved in coding noxious stimuli. Specifically, I will present evidence in support of the hypothesis that the phenomenon of central pain may be the result of suppressed inhibitory regulation of POm activity.