Faculty Bibliography

Both the thalamocortical and limbic systems generate a variety of brain state-dependent rhythms but the relationship between the oscillatory families is not well understood. Transfer of information across structures can be controlled by the offset oscillations. We suggest that slow oscillation of the neocortex, which was discovered by Mircea Steriade, temporally coordinates the self-organized oscillations in the neocortex, entorhinal cortex, subiculum and hippocampus. Transient coupling between rhythms can guide bidirectional information transfer among these structures and might serve to consolidate memory traces

Quantitative determination of cerebral blood volume (CBV) is important for understanding brain physiology and pathophysiology. In this work, a novel approach is presented for accurate measurement of absolute CBV (aCBV) using vascular-space-occupancy (VASO) MRI, a blood-nulling pulse sequence, in combination with the T(1) shortening property of Gd-DTPA. Two VASO images with identical imaging parameters are acquired before and after contrast agent injection, resulting in a subtracted image that reflects the amount of blood present in the brain, i.e., CBV. With an additional normalizing factor, aCBV in units of milliliters of blood per 100 mL of brain can be estimated. Experimental results at 1.5 and 3 T systems showed that aCBV maps with high spatial resolution can be obtained with high reproducibility. The averaged aCBV values in gray and white matter were 5.5 +/- 0.2 and 1.4 +/- 0.1 mL of blood/100 mL of brain, respectively. Compared to dynamic susceptibility contrast techniques, VASO MRI is based upon a relatively straightforward theory and the calculation of CBV does not require measurement of an arterial input function. In comparison with previous pre/postcontrast difference approaches, VASO MRI provides maximal signal difference between pre- and postcontrast situation and does not require the use of whole blood for signal normalization

The tilt aftereffect (TAE) is a visual illusion in which prolonged adaptation to an oriented stimulus causes shifts in subsequent perceived orientations. Historically, neural models of the TAE have explained it as the outcome of response suppression of neurons tuned to the adapting orientation. Recent physiological studies of neurons in primary visual cortex (V1) have confirmed that such response suppression exists. However, it was also found that the preferred orientations of neurons shift away from the adapting orientation. Here we show that adding this second factor to a population coding model of V1 improves the correspondence between neurophysiological data and TAE measurements. According to our model, the shifts in preferred orientation have the opposite effect as response suppression, reducing the magnitude of the TAE.

A ubiquitous feature of the vertebrate anatomy is the segregation of the brain into white and gray matter. Assuming that evolution maximized brain functionality, what is the reason for such segregation? To answer this question, we posit that brain functionality requires high interconnectivity and short conduction delays. Based on this assumption we searched for the optimal brain architecture by comparing different candidate designs. We found that the optimal design depends on the number of neurons, interneuronal connectivity, and axon diameter. In particular, the requirement to connect neurons with many fast axons drives the segregation of the brain into white and gray matter. These results provide a possible explanation for the structure of various regions of the vertebrate brain, such as the mammalian neocortex and neostriatum, the avian telencephalon, and the spinal cord.

Interneurons of the cerebral cortex represent a heterogeneous population of cells with important roles in network function. At present, little is known about how these neurons are specified in the developing telencephalon. To explore whether this diversity is established in the early progenitor populations, we conducted in utero fate-mapping of the mouse medial and caudal ganglionic eminences (MGE and CGE, respectively), from which most cortical interneurons arise. Mature interneuron subtypes were assessed by electrophysiological and immunological analysis, as well as by morphological reconstruction. At E13.5, the MGE gives rise to fast-spiking (FS) interneurons, whereas the CGE generates predominantly regular-spiking interneurons (RSNP). Later at E15.5, the CGE produces RSNP classes distinct from those generated from the E13.5 CGE. Thus, we provide evidence that the spatial and temporal origin of interneuron precursors in the developing telencephalic eminences predicts the intrinsic physiological properties of mature interneurons

Sensory encoding in spiking neurons depends on both the integration of sensory inputs and the intrinsic dynamics and variability of spike generation. We show that the stimulus selectivity, reliability, and timing precision of primate retinal ganglion cell (RGC) light responses can be reproduced accurately with a simple model consisting of a leaky integrate-and-fire spike generator driven by a linearly filtered stimulus, a postspike current, and a Gaussian noise current. We fit model parameters for individual RGCs by maximizing the likelihood of observed spike responses to a stochastic visual stimulus. Although compact, the fitted model predicts the detailed time structure of responses to novel stimuli, accurately capturing the interaction between the spiking history and sensory stimulus selectivity. The model also accounts for the variability in responses to repeated stimuli, even when fit to data from a single (nonrepeating) stimulus sequence. Finally, the model can be used to derive an explicit, maximum-likelihood decoding rule for neural spike trains, thus providing a tool for assessing the limitations that spiking variability imposes on sensory performance

Systemic delivery of (1R-1-benzo thiophen-5-yl-2[2-diethylamino)-ethoxy] ethanol hydrochloride (T-588) prevented long-term depression (LTD) of the parallel fiber (PF)-Purkinje cell (PC) synapse induced by conjunctive climbing fiber and PF stimulation in vivo. However, similar concentrations of T-588 in the brains of behaving mice and rats affected neither motor learning in the rotorod test nor the learning of motor timing during classical conditioning of the eyeblink reflex. Rats given doses of T-588 that prevented PF-PC LTD were as proficient as controls in learning to adapt the timing of their conditioned eyeblink response to a 150- or 350-ms change in the timing of the paradigm. The experiment indicates that PF-PC LTD under control of the climbing fibers is not required for general motor adaptation or the learning of response timing in two common models of motor learning for which the cerebellum has been implicated. Alternative mechanisms for motor timing and possible functions for LTD in protection from excitotoxicity are discussed

Long-term depression (LTD) of the parallel-fiber (PF) Purkinje synapse induced by four different experimental paradigms could be prevented in rat cerebellar slices by T-588, a neuroprotective compound. The paradigms consisted of pairing PF activation with climbing-fiber activation, direct depolarization, glutamic iontophoretic depolarization, or caffeine. In all cases, LTD was determined by patch-clamp recording of PF excitatory postsynaptic currents at the Purkinje cell somata. T-588 at 1 muM prevented the triggering of LTD reversibly and did not generate LTD on its own. Two-photon calcium-sensitive dye imaging demonstrated that T-588 reduces intracellular calcium concentration ([Ca(2+)](i)) increase by blocking calcium release from intracellular stores. Because [Ca(2+)](i) increase has been widely shown to trigger LTD and glutamate excitotoxicity, we propose that LTD may act as a neuroprotective mechanism. As such, LTD would serve to decrease glutamatergic-receptor sensitivity to limit deleterious [Ca(2+)](i) increase rather than to act as a mechanism for cerebellar learning