Acuity-sensitivity trade-offs of X and Y cells in the cat lateral geniculate complex: role of the medial interlaminar nucleus in scotopic vision.

1. The cat medial interlaminar nucleus (MIN) receives inputs almost exclusively from tapetal retina, suggesting that the MIN has a special role in dim-light vision. In this study we compared the sensitivities of cells in the MIN with those in layers A and magnocellular C of the lateral geniculate nucleus (LGNd), using drifting sinusoidal gratings to determine contrast thresholds as a function of spatial frequency and retinal adaptation level over the entire scotopic range. 2. About one-half of the cells recorded in the MIN and layer A had brisk responses that could be nulled by properly positioned, counterphased sinusoidal gratings, and were classified as X cells. The rest of the cells in the MIN and layer A, as well as all cells recorded in layer C, were Y cells. 3. MIN cells had higher contrast sensitivity than layer A cells for low spatial frequencies (0.15 cycles/deg and below) over a wide range of adaptation levels, both overall and for separate comparisons within X or Y cells. Layer C Y cells were intermediate in sensitivity between MIN and layer A Y cells. For low spatial frequencies, Y cells as a group were more sensitive than X cells, whereas the reverse was true for high spatial frequencies. 4. These data enable one to determine the lowest adaptation level at which stimuli of a given contrast can be detected for a given structure. At the lowest spatial frequencies, the MIN can function at adaptation levels approximately 1 log unit below layer A, averaged over all stimulus contrasts. In contrast, the tapetum lowers luminance threshold by at most 0.16 log unit. 5. For scotopic conditions and eccentricities within 15 degrees of the area centralis, contrast sensitivity decreases with eccentricity for low spatial frequencies and remains flat or slightly increases for high spatial frequencies. This relationship, which is opposite to that found for photopic vision, is strongest for MIN Y cells. 6. These data support the hypothesis that the retinal conflict between sensitivity and acuity is ameliorated in the CNS through separate thalamic relays with different degrees of afferent convergence. MIN cells have higher luminance sensitivity than layer A cells, but at the expense of acuity. Layer C appears to occupy an intermediate position in this trade-off.     

Functional specificity of lateral geniculate nucleus laminae of the rhesus monkey.

1. This study investigated the functional specificity of the lateral geniculate mucleus (LGN) of the rhesus monkey using microelectrode-recording techniques. 2. The parvocellular laminae of the LGN receive input predominantly from medium-conduction-velocity optic tract fibers, while the magnocellular laminae receive fast-conducting axons from the retina. 3. Cells projecting from the parvocellular layers to area 17 have medium-conduction velocities, while those from the magnocellular layers are fast conducting. 4. The majority of cells in the parvocellular layers have a concentric color-opponent receptive-field organization. The receptive fields of magnocellular layers cells are also concentrically organized, but their center-surround organization is independent of wavelength. 5. Responses in the parvocellular layers are more sustained than in the magnocellular layers. 6. Cells in the dorsal pair of parvocellular layers are predominantly on-center. In the ventral pair of parvocellular layers, most cells are off-center. 7. Blue-selective cells are found predominantly in the ventral pair of parvocellular layers. All of these found gave on-responses to blue stimuli.     

Cat area 17. I. Pattern of thalamic control of cortical layers

Reversible inactivation of individual layers of the cat lateral geniculate and medial interlaminar nuclei was used to investigate the necessary and sufficient inputs for maintaining visually driven activity and receptive field properties in area 17. Neither orientation selectivity nor direction selectivity depends on any individual geniculate layer. We identified two groups of cortical layers on the basis of the pattern of thalamic inputs providing visual driving through the contralateral eye. One group, consisting of layers 4 and 6, has geniculate layer A as its only necessary and sufficient input. The other, consisting of supragranular layers, integrates at least two sufficient thalamic inputs, one of which is layer A. Several major receptive field properties are independently generated in these two groups of layers.     

Cat area 17. IV. Two types of corticotectal cells defined by controlling geniculate inputs

The dependence of cat area 17 corticotectal (CT) cells on specific subdivisions of the dorsal lateral geniculate (LGN) and medial interlaminar nuclei (MIN) was examined using reversible inactivation techniques. Inactivation of layer C of the LGN or layer 1 of the MIN did not block visual activity of CT cells driven through the contralateral eye. Inactivation of layer A of the LGN revealed two populations of CT cells: one strongly dependent on layer A and one whose visually driven activity survived layer A inactivation. CT cells that responded best to short stimuli (special complex cells) were least dependent on layer A, whereas cells that responded best to long stimuli (standard complex cells) were most dependent on layer A. We propose a model of the intracortical circuitry of these two types of CT cells. Standard complex cells, which are heavily dependent on layer A, receive sustaining visual input through layers 4 and/or 6. Special complex cells, which are not dependent on any single layer of the lateral geniculate nucleus, receive sustaining visual input from supragranular layers.     

A method of reversible inactivation of small regions of brain tissue.

A method is described for reversibly inactivating small, precisely localized regions of brain tissue with injections of nanoliter quantities of the local anesthetic lidocaine hydrochloride. The injections are made through a combined recording-injection probe consisting of a glass micropipette onto whose outer surface is plated a metallic cylinder for recording extracellular action potentials. The recording cylinder for recording extracellular action potentials. The recording cylinder, located a known distance from the pipette tip, picks up a continuous, large-amplitude, multiunit response which can be used to accurately position the tip according to physiological criteria. It also provides a means of determining the duration of the anesthetic block and estimating its spreat. This devise has been used to selectively block 200--400 micrometers regions of individual laminae of the lateral geniculate nucleus centered within 50 micrometers of a retinotopically defined target site. The blocks last from 3 to 10 min and can be repeated many times at the same location.     

Role of stromal cell-mediated Notch signaling in CLL resistance to chemotherapy

Stromal cells are essential components of the bone marrow (BM) microenvironment that regulate and support the survival of different tumors, including chronic lymphocytic leukemia (CLL). In this study, we investigated the role of Notch signaling in the promotion of survival and chemoresistance of human CLL cells in coculture with human BM-mesenchymal stromal cells (hBM-MSCs) of both autologous and allogeneic origin. The presence of BM-MSCs rescued CLL cells from apoptosis both spontaneously and following induction with various drugs, including Fludarabine, Cyclophosphamide, Bendamustine, Prednisone and Hydrocortisone. The treatment with a combination of anti-Notch-1, Notch-2 and Notch-4 antibodies or γ-secretase inhibitor XII (GSI XII) reverted this protective effect by day 3, even in presence of the above-mentioned drugs. Overall, our findings show that stromal cell-mediated Notch-1, Notch-2 and Notch-4 signaling has a role in CLL survival and resistance to chemotherapy. Therefore, its blocking could be an additional tool to overcome drug resistance and improve the therapeutic strategies for CLL.     

Endothelin receptor antagonism prevents hypoxia-induced mortality and morbidity in a mouse model of sickle-cell disease

Patients with sickle-cell disease (SCD) suffer from tissue damage and life-threatening complications caused by vasoocclusive crisis (VOC). Endothelin receptors (ETRs) are mediators of one of the most potent vasoconstrictor pathways in mammals, but the relationship between vasoconstriction and VOC is not well understood. We report here that pharmacological inhibition of ETRs prevented hypoxia-induced acute VOC and organ damage in a mouse model of SCD. An in vivo ultrasonographic study of renal hemodynamics showed a substantial increase in endothelin-mediated vascular resistance during hypoxia/reoxygenation-induced VOC. This increase was reversed by administration of the dual ETR antagonist (ETRA) bosentan, which had pleiotropic beneficial effects in vivo. It prevented renal and pulmonary microvascular congestion, systemic inflammation, dense rbc formation, and infiltration of activated neutrophils into tissues with subsequent nitrative stress. Bosentan also prevented death of sickle-cell mice exposed to a severe hypoxic challenge. These findings in mice suggest that ETRA could be a potential new therapy for SCD, as it may prevent acute VOC and limit organ damage in sickle-cell patients.     

Reversible inactivation of subcortical sites by drug injection

Reversible inactivation of subcortical targets by means of drug injections has been a powerful tool for revealing the contributions of discrete brain structures to behavior and the functional organization of the brain. This paper is intended to provide practical advice on this approach, including the choice of drug, means of delivering drugs, strategies for evaluating the action of injected drugs, and the application of this method to experiments with awake animals.     

Spectrally resolved neurophotonics: a case report of hemodynamics and vascular components in the mammalian brain

We developed a spectral technique that is independent of the light transport modality (diffusive or nondiffusive) to separate optical changes in scattering and absorption in the cat's brain due to the hemodynamic signal following visual stimulation. We observe changes in oxyhemoglobin and deoxyhemoglobin concentration signals during visual stimulation reminiscent of the functional magnetic resonance imaging (fMRI) blood oxygenation level dependence (BOLD) effect. Repeated measurements at different locations show that the observed changes are local rather than global. We also determine that there is an apparent large decrease in the water concentration and scattering coefficient during stimulation. We model the apparent change in water concentration on the separation of the optical signal from two tissue compartments. One opaque compartment is featureless (black), due to relatively large blood vessels. The other compartment is the rest of the tissue. When blood flow increases due to stimulation, the opaque compartment increases in volume, resulting in an overall decrease of tissue transmission. This increase in baseline absorption changes the apparent relative proportion of all tissue components. However, due to physiological effects, the deoxyhemoglobin is exchanged with oxyhemoglobin resulting in an overall increase in the oxyhemoglobin signal, which is the only component that shows an apparent increase during stimulation.