Faculty Bibliography

Granule cell (GC) neurogenesis increases following seizures, and some newborn GCs develop in abnormal locations within the hilus. These ectopic GCs (EGCs) display robust spontaneous and evoked excitatory activity. However, the pattern of afferent input they receive has not been fully defined. This study used electron microscopic immunolabeling to quantitatively evaluate mossy fiber (MF) input to EGCs since MFs densely innervate the hilus normally and undergo sprouting in many animal models of epilepsy. EGC dendrites were examined in tissue from epileptic rats that had initially been treated with pilocarpine to induce status epilepticus and subsequently had spontaneous seizures. MF terminals were labeled with a zinc transporter-3 antibody, and calbindin immunoreactivity was used to label hilar EGCs and GC layer GCs. The pattern of input provided by sprouted MF terminals to EGC dendrites was then compared to the pattern of MF input to GC dendrites in the inner molecular layer (IML), where most sprouted fibers are thought to project. Analysis of EGC dendrites demonstrated that MF terminals represented their predominant source of afferent input: they comprised 63% of all terminals and, on average, occupied 40% and 29% of the dendritic surface in the dorsal and ventral dentate gyrus, respectively, forming frequent synapses. These measures of connectivity were significantly greater than comparable values for MF innervation of GC dendrites located in the IML of the same tissue sections. Thus, EGCs develop a pattern of synaptic connections that could help explain their previously identified predisposition to discharge in epileptiform bursts and suggest that they play an important role in the generation of seizure activity in the dentate gyrus

Myocardial perfusion can be estimated, in principle, from first-pass MR images by converting the T(1)-weighted signal-time curves to contrast agent concentration-time curves. Typically, T(1) weighting is achieved by saturating the magnetization with a nonselective radiofrequency (RF) pulse prior to the imaging sequence. The accuracy of the perfusion estimate derived from the single-point T(1)-weighted signal depends on the initial residual longitudinal magnetization (RLM) produced by the saturation pulse. In this study we demonstrate that single-shot, echo-planar imaging can be used to show initial RLM resulting from incomplete saturation due to static magnetic field and RF field inhomogeneities in the heart at 1.5 T. Three saturation pulses, single, composite simple, and composite B(1)-insensitive rotation (BIR-4) were evaluated in phantom and cardiac experiments. The RLM image was calculated by normalizing the saturated image by a proton-density-weighted image. Mean RLM produced by the three saturation pulses was significantly different in noncontrast cardiac imaging (RLM(single) = 0.108 +/- 0.078; RLM(composite) = 0.051 +/- 0.052; RLM(BIR-4) = 0.011 +/- 0.009; P < 0.001; n = 20). Using a BIR-4 pulse to perform saturation of magnetization seems promising for improving the effectiveness and uniformity of T(1) weighting for first-pass perfusion imaging

The nodes of Ranvier are regularly spaced gaps between myelin sheaths that are markedly enriched in voltage-gated sodium channels and associated proteins. Myelinating glia play a key role in promoting node formation, although the requisite glial signals remain poorly understood. In this study, we have examined the expression of glial proteoglycans in the peripheral and central nodes. We report that the heparan sulfate proteoglycan, syndecan-3, becomes highly enriched with PNS node formation; its ligand, collagen V, is also concentrated at the PNS nodes and at lower levels along the abaxonal membrane. The V1 isoform of versican, a chondroitin sulfate proteoglycan, is also present in the nodal gap. By contrast, CNS nodes are enriched in versican isoform V2, but not syndecan-3. We have examined the molecular composition of the PNS nodes in syndecan-3 knockout mice. Nodal components are normally expressed in mice deficient in syndecan-3, suggesting that it has a nonessential role in the organization of nodes in the adult. These results indicate that the molecular composition and extracellular environment of the PNS and CNS nodes of Ranvier are significantly distinct

The pericardium, although seldom the primary cause of systemic illness, can be involved in almost every type of disease. Pericardial involvement may be subtle and escape detection unless specifically sought, or it can overshadow features of the underlying systemic disease. Suspected pericardial disease is usually initially evaluated with echocardiography. However, magnetic resonance imaging can offer additional valuable information. In addition to the excellent resolution and unlimited imaging planes available for visualization of the entire pericardial sac, the wide field of view allows for evaluation of involvement of adjacent cardiac structures. Dynamic functional imaging and tissue characterization with and without contrast can further characterize disease and provide information regarding concomitant myocardial disease and effects on cardiac motion. The treatment of specific pericardial conditions ultimately depends on the underlying disease process. Magnetic resonance imaging can provide useful information to aid in diagnosis, management, and guidance of therapy for pericardial disease

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system that is the most common cause of nontraumatic disability in young adults in the United States. In recent years, magnetic resonance imaging (MRI) has been established as an important paraclinical tool in MS for the assessment of clinical diagnosis, natural history, and treatment effects. In MS studies, there are many advantages to having a sensitive and reliable in vivo method for investigating the specific pathological changes of white matter and its integrity during the disease process. As a consequence, in the past decade, the application of MRI to the study of MS has been explored from conventional MRI to new advanced quantitative techniques with greater pathological specificity and sensitivity. Diffusion tensor imaging (DTI) is one of the most promising techniques with regard to MS. It quantifies the amount of nonrandom water diffusion within tissues and provides unique in vivo information about the pathological processes that affect water diffusion as a result of brain microstructural damage. This review outlines the current state of the art and future direction of DTI and fiber tractography in the study of MS disease

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.

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