Harold Burton - US grants

Several cytoarchitectonic areas can be distinguished along the cortex buried within he Sylvain fissure in primates and amongst these, cutaneous stimulation activates neurons in the second somatosensory area (SII), retroinsular cortex (Ri), granular insula (Ig) and a portion of area 7 (7b). The objectives for this project are 1) to determine the best tactile stimulus for neurons in these cortical loci by analyzing quantitatively responses to controlled mechanical stimuli including different frequencies of vibrotactile stimulation; 2) to examine neuronal activity to sinusoidal tactile stimulation when the probe tip size is changed, when rigid surrounds encircle the stimulation site, and when the receptive field is first exposed to conditioning mechanical stimulation of different frequencies; 3) to study the effects of conditioning electrical stimulation of SI on neuronal responses in SII; and 4) to record the neuronal responses in these regions in animals behaviorally conditioned to perceive various somatosensory stimuli under different expectancy conditions. These studies may further define the function of SII and the surrounding areas in somesthesis and may indicate why destruction of these areas in primates leads to alteration in attention to somesthetic stimuli.

Several experiments are proposed to elucidate the functional role of inhibitory GABAergic circuits in primary and secondary somatic sensory cortex of cats. This will be accomplished by recording individual neuronal respnoses to servo-controlled tactile stimuli before, during, and after microiontophoretic applicaton of drugs (e.g., bicculline) that selectively block post-synaptic GABA receptors. The first experiment will investigate how GABAergic activity influences the spatial organization of cortical receptive fields by measuring changes in the magnitude of neuronal responses to stimuli of different indentation amplitudes at different receptive field positions. This experiment will study drug induced changes in the summated response profiles. A second experiment will examine stimulus-response functions to vibratory stimuli and will determine whether cells with phasic responses to a sustained vibration show sustained periodically entrained discharges when GABA receptors are blocked and whether GABAergic transmission influences the range of frequencies of vibratory stimuli that can activate a cortical cell. A final experiment will examine the role of GABAergic circuits in controlling convergence and integration of inputs from different peripheral mechanoreceptors. A condition-test paradigm will be used to determine if a neuron's response to a preferred range of vibratory frequencies is altered by the simultaneous presence of a second, conditioning vibration that is applied near the cutaneous site of the test stimulus either within or near the receptive field of the cell. The conditioning vibrations are to be applied in the preferred or non-preferred range of frequencies and thereby activate the same or a different population of peripheral receptors then are associated with the optimal vibration frequency being applied through the test stimulus. Collectively, these experments will indicate possible contributions of GABAergic circuits to the interplay of afferent activity that determines a cortical cell's responsiveness and the range of peripheral receptors that influence its activity. These results should indicate, more generally, the role of GABAergic inhibitory circuits in the unique neuronal responses that characterize SI and SII.

Several experiments are proposed to elucidate the functional role of inhibitory GABAergic circuits in primary and secondary somatic sensory cortex of cats. This will be accomplished by recording individual neuronal respnoses to servo-controlled tactile stimuli before, during, and after microiontophoretic applicaton of drugs (e.g., bicculline) that selectively block post-synaptic GABA receptors. The first experiment will investigate how GABAergic activity influences the spatial organization of cortical receptive fields by measuring changes in the magnitude of neuronal responses to stimuli of different indentation amplitudes at different receptive field positions. This experiment will study drug induced changes in the summated response profiles. A second experiment will examine stimulus-response functions to vibratory stimuli and will determine whether cells with phasic responses to a sustained vibration show sustained periodically entrained discharges when GABA receptors are blocked and whether GABAergic transmission influences the range of frequencies of vibratory stimuli that can activate a cortical cell. A final experiment will examine the role of GABAergic circuits in controlling convergence and integration of inputs from different peripheral mechanoreceptors. A condition-test paradigm will be used to determine if a neuron's response to a preferred range of vibratory frequencies is altered by the simultaneous presence of a second, conditioning vibration that is applied near the cutaneous site of the test stimulus either within or near the receptive field of the cell. The conditioning vibrations are to be applied in the preferred or non-preferred range of frequencies and thereby activate the same or a different population of peripheral receptors then are associated with the optimal vibration frequency being applied through the test stimulus. Collectively, these experments will indicate possible contributions of GABAergic circuits to the interplay of afferent activity that determines a cortical cell's responsiveness and the range of peripheral receptors that influence its activity. These results should indicate, more generally, the role of GABAergic inhibitory circuits in the unique neuronal responses that characterize SI and SII.

This research focuses on the characterization of the dimensions and function of the microvessels in regenerated skeletal muscle. The model to be used is the grafted retractor muscle in the hamster. The muscle is removed, placed in a myotoxic solution and grafted into its original position. All of the original fibers, blood vessels and nerves are destroyed by this process. The muscle fibers regenerate and the graft is revascularized by the ingrowth of vessels from the surrounding tissue. The microvasculature of the muscle graft will be observed at different times between 30 and 270 days, by the use of in vivo video-microscopy. The muscle graft is isolated, exposed and superfused with a bicarbonate buffered physiological salt solution. Responses of the microvessels to various topically applied or infused substances are taped and replayed for direct measurement from a television monitor. The study is divided into 3 parts: 1. The description of the microvascular dimensions (arteriole, capillary and venule length and diameters) and the orientation of capillaries; 2. The response (change in diameter) of arterioles to vasoactive substances that a) act on the smooth muscle and are either receptor mediated (norepinephrine, adenosine, and prostaglandin E1) or non-receptor mediated (verapamil, potassium), or b) are dependent upon an intact endothelium for their actions (acetlycholine, Calcium ionophore A23187, and Substance P); 3. The measurement of the relative permeability of post-capillary venules to selected substances that are either receptor mediated (histamine and bradykinin), non-receptor mediated (phospholipase A2 and Calcium ionophore A 23187) or somehow alter the macromolecular organization of the endothelial cell surface (protamine sulfate and Evans blue dye). This research will elucidate some of the mechanisms that underlie the alterations in microvessel function and blood flow characteristics that accompany skeletal muscle degeneration and regeneration following injury. This will lead to a better understanding of performance and fatigability of skeletal muscle that has been damaged and repaired and may help in the development of intervention and/or rehabilitation strategies of injuries associated with ischemia, trauma, disease, myotoxic agents and strenuous exercise.

Several cytoarchitectonic areas can be distinguished along the cortex buried within he Sylvain fissure in primates and amongst these, cutaneous stimulation activates neurons in the second somatosensory area (SII), retroinsular cortex (Ri), granular insula (Ig) and a portion of area 7 (7b). The objectives for this project are 1) to determine the best tactile stimulus for neurons in these cortical loci by analyzing quantitatively responses to controlled mechanical stimuli including different frequencies of vibrotactile stimulation; 2) to examine neuronal activity to sinusoidal tactile stimulation when the probe tip size is changed, when rigid surrounds encircle the stimulation site, and when the receptive field is first exposed to conditioning mechanical stimulation of different frequencies; 3) to study the effects of conditioning electrical stimulation of SI on neuronal responses in SII; and 4) to record the neuronal responses in these regions in animals behaviorally conditioned to perceive various somatosensory stimuli under different expectancy conditions. These studies may further define the function of SII and the surrounding areas in somesthesis and may indicate why destruction of these areas in primates leads to alteration in attention to somesthetic stimuli.

DESCRIPTION: (adapted from applicant's abstract)Braille reading is a remarkable example of the human brain adopting compensatory strategies following loss of a vital function, namely visual input to language. We propose using whole-brain functional magnetic resonance imaging (fMRI) in congenitally blind, late-onset blind and sighted subjects to investigate the functional anatomy of the sensory and cognitive processes underlying Braille reading. These studies address an on-going debate about whether the blind show increased capacity for processing non-visual information and whether these changes are examples of the brain's adaptive plasticity. The central issue underlying these experiments is investigating possible changes in somatosensory, visual and language areas of the brain that facilitate fluent Braille reading in the blind. We propose six interlocking experiments that involve, in turn, passive somatosensory, active tactile (haptic) and language tasks. The first two experiments focus on responses to passive, controlled somatosensory stimulation in blind vs. sighted subjects. These studies involve tactile discrimination tasks and a low-level lexical task of identifying raised block capital letters. The middle two experiments study blind subjects actively reading Braille, first with an emphasis on haptic pattern recognition and then higher-level semantics (word meaning). The last two experiments again involve blind and sighted subjects, now performing semantic and phoneme (word sound)tasks in response to heard words. The first and last two experiments examine similarities and differences in the organization of sensory and language systems in blind and sighted subjects performing non-Braille tasks, without visual and motor performance bias. In addition, these experiments will determine whether Braille reading skill reflects functional cortical changes that are general to somatosensory processing or specific to Braille reading and whether blind and sighted subjects use visual cortex for non-visual tasks in a similar manner. The middle two experiments investigate language skills unique to the blind to determine whether theses subjects have fundamentally modified neural systems or instead access the same cognitive systems as sighted subjects by a different sensory route.