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M E Diamond

Publications and source records attributed to M E Diamond.

34 records · Page 2Linked to original sources

[Functional mapping of the motor and primary sensorial cortex using magnetic resonance techniques. I. Preliminary data].

Functional Magnetic Resonance Imaging (fMRI) techniques sensitive to the local changes in blood flow, volume and oxygenation accompanying neuronal activation are powerful tools to investigate the human brain function. Experiments were performed on 10 right-handed healthy volunteers (age range: 20-39 years), using a 1.5 T whole-body MRI system. Two oblique contiguous planes were investigated along the central sulcus of the left hemisphere. Functional images were acquired using a Gradient Echo sequence while the subjects repetitively performed sequential finger to thumb opposition movements of the right hand or mental imagery of a visual scene. Twelve images for each task were obtained over a 6-min experimental period; they were then analyzed with the software provided by the manufacturer. In all the subjects small areas were activated in both the precentral and postcentral gyrus, mean percentage signal increases during finger movement being 10.7% and 3.8%, respectively. These values are fairly higher than literature ones. However several factors, such as voxel volume, are involved in determining the measured signal increase during activation. Moreover, in most cases the software procedures provided with the MR equipment to analyze the functional images imply subjective choices. It is thus necessary to implement new software packages for the analysis of fMRI images to apply more appropriate statistical procedures and to obtain more homogeneous and objective final information.

Adult↗

Allelic differences in the VHOx-1 gene explain the absence of a B cell clonal dominance in the primary response of C57BL/6 mice to phthalate.

A highly conserved Id (CRIXmp-1) associated with the murine (BALB/c) humoral immune response to the hapten phthalate (Xmp) is conspicuously absent in C57BL/6 mice. The absence of this Id in C57BL/6 mice is shown here to be due to the absence of the appropriate VH gene (VHOx-1) usage in the Xmp response. To determine whether the failure to utilize this VH was due to an active suppression or to the lack of the requisite VH gene in the available repertoire, VHOx-1 gene-specific primers were used to amplify the germ-line VHOx-1 gene from genomic DNA from BALB/c and C57BL/6 mice. The germ-line coding sequence of the C57BL/6 allele of the VHOx-1 gene is 99% similar to the germ-line coding sequence of the BALB/c allele. Amplification of cDNA made from splenic RNA from C57BL/6 mice confirmed that this gene is expressed. There are four nucleotide differences that lead to three amino acid changes in the predicted protein sequence. Each change is either in or immediately adjacent to a complementarity-determining region (CDR). Two of these changes are unique to the C57BL/6 allele and are not shared with CRIXmp-1-expressing strains. These two changes are predicted to alter the Xmp binding capabilities of the C57BL/6 allelic form of this VH gene, thereby explaining the absence of the Xmp-1 clonotype, which is dominant in the primary Xmp immune response of most other strains of mice.

Alleles↗

Laminar comparison of somatosensory cortical plasticity.

During tactile learning there is a transformation in the way the primary somatosensory cortex integrates, represents, and distributes information from the skin. To define this transformation, the site of earliest modification has been identified in rat somatosensory cortex after a change in sensory experience. Afferent activity was manipulated by clipping all except two whiskers on one side of the snout ("whisker pairing"), and the receptive fields of neurons at different cortical depths were mapped 24 hours later. Neurons in layer IV, the target of the primary thalamic pathway, were unaltered, whereas neurons located above and below layer IV showed significant changes. These changes were similar to those that occur in layer IV after longer periods of whisker pairing. The findings support the hypothesis that the layers of cortex contribute differently to plasticity. Neurons in the supragranular and infragranular layers respond rapidly to changes in sensory experience and may contribute to subsequent modification in layer IV.

Action Potentials↗

Dynamic synaptic modification threshold: computational model of experience-dependent plasticity in adult rat barrel cortex.

Previous electrophysiological experiments have documented the response of neurons in the adult rat somatic sensory ("barrel") cortex to whisker movement after normal experience and after periods of experience with all but two whiskers trimmed close to the face (whisker "pairing"). To better understand how the barrel cortex adapts to changes in the flow of sensory activity, we have developed a computational model of a single representative barrel cell based on the Bienenstock, Cooper, and Munro (BCM) theory of synaptic plasticity. The hallmark of the BCM theory is the dynamic synaptic modification threshold, theta M, which dictates whether a neuron's activity at any given instant will lead to strengthening or weakening of the synapses impinging on it. The threshold theta M is proportional to the neuron's activity averaged over some recent past. Whisker pairing was simulated by setting input activities of the cell to the noise level, except for two inputs that represented untrimmed whiskers. Initially low levels of cell activity, resulting from whisker trimming, led to low values for theta M. As certain synaptic weights potentiated, due to the activity of the paired inputs, the values of theta M increased and after some time their mean reached an asymptotic value. This saturation of theta M led to the depression of some inputs that were originally potentiated. The changes in cell response generated by the model replicated those observed in in vivo experiments. Previously, the BCM theory has explained salient features of developmental experience-dependent plasticity in kitten visual cortex. Our results suggest that the idea of a dynamic synaptic modification threshold, theta M, is general enough to explain plasticity in different species, in different sensory systems, and at different stages of brain maturity.

Animals↗

An innocuous bias in whisker use in adult rats modifies receptive fields of barrel cortex neurons.

The effect of innocuously biasing the flow of sensory activity from the whiskers for periods of 3-30 d in awake, behaving adult rats on the receptive field organization of rat SI barrel cortex neurons was studied. One pair of adjacent whiskers, D2 and either D1 or D3, remained intact unilaterally (whisker pairing), all others being trimmed throughout the period of altered sensation. Receptive fields of single cells in the contralateral D2 barrel were analyzed under urethane anesthesia by peristimulus time histogram (PSTH) and latency histogram analysis after 3, 7-10, and 30 d of pairing and compared with controls, testing all whiskers cut to the same length. Response magnitudes to surround receptive field in-row whiskers D1 and D3 were not significantly different for control animals. The same was found for surround in-arc whiskers C2 and E2. However, after 3 d of whisker pairing a profound bias occurred in response to the paired D-row surround whisker relative to the opposite trimmed surround D-row whisker and to the C2 and E2 whiskers. This bias increased with the duration of pairing, regardless of which surround whisker (D1 or D3) was paired with D2. For all three periods of pairing the mean response to the paired surround whisker was increased relative to controls, but peaked at 7-10 d. Response to the principal center-receptive (D2) whisker was increased for the 3 and 7-10 d groups and then decreased at 30 d. Responses to trimmed arc surround whiskers (C2 and E2) were decreased in proportion to the duration of changed experience. Analysis of PSTH data showed that earliest discharges (5-10 msec poststimulus) to the D2 whisker increased progressively in magnitude with duration of pairing. For the paired surround whisker similar early discharges newly appeared after 30 d of pairing. At 3 and 7-10 d of pairing, increases in response to paired whiskers and decreases to cut surround whiskers were confined to late portions of the PSTH (10-100 msec poststimulus). Changes at 3-10 d can be attributed to alterations in intracortical synaptic relay between barrels. Longer-term changes in response to both paired whisker inputs (30 d) largely appear to reflect increases in thalamocortical synaptic efficacy. Our findings suggest that novel innocuous somatosensory experiences produce changes in the receptive field configuration of cortical cells that are consistent with Hebbian theories of experience-dependent potentiation and weakening of synaptic efficacy within SI neocortical circuitry, for correlated and uncorrelated sensory inputs, respectively.

Animals↗

Experience-dependent plasticity in adult rat barrel cortex.

This study tested the hypothesis that the receptive fields (RFs) of neurons in the adult sensory cortex are shaped by the recent history of sensory experience. Sensory experience was altered by a brief period of "whisker pairing": whiskers D2 and either D1 or D3 were left intact, while all other whiskers on the right side of the face were trimmed close to the fur. The animals were anesthetized 64-66 h later and the responses of single neurons in contralateral cortical barrel D2 to stimulation of whisker D2 (the center RF) and the four neighboring whiskers (D1, D3, C2, and E2; the excitatory surround RF) were measured. Data from 79 cells in four rats with whiskers paired were compared to data from 52 cells in four rats with untrimmed whiskers (control cases). During the period of whisker pairing, the RFs of cells in barrel D2 changed in three ways: (i) the response to the center RF, whisker D2, increased by 39%, (ii) the response to the paired surround RF whisker increased by 85-100%, and (iii) the response to all clipped (unpaired) surround RF whiskers decreased by 9-42%. In the control condition, the response of barrel D2 cells to the two neighboring whiskers, D1 and D3, was equal. After whisker pairing, the response to the paired neighbor of D2 was more than twice as large as the response to the cut neighbor of D2. These findings indicate that a brief change in the pattern of sensory activity can alter the configuration of cortical RFs, even in adult animals.

Animals↗

Somatic sensory responses in the rostral sector of the posterior group (POm) and in the ventral posterior medial nucleus (VPM) of the rat thalamus: dependence on the barrel field cortex.

The projection from the whiskers of the rat to the S-I (barrel) cortex is segregated into two separate pathways--a lemniscal pathway relayed by the ventral posterior medial nucleus (VPM) to cortical barrels, and a paralemniscal pathway relayed by the rostral sector of the posterior complex (POm) to the matrix between, above, and below barrels. Before investigating how the barrel cortex integrates these sensory pathways, it is important to learn more about the influence of the various inputs to the two thalamic nuclei. Based on the greater density of descending versus ascending projections to POm, it seemed likely that corticofugal inputs play an important role in the sensory activity of POm. To test this, the responses of POm and VPM cells to sensory stimuli were measured before, during, and after suppression of the S-I cortex. S-I was suppressed by application of magnesium or by cooling; the status of the barrel cortex was assessed continuously by an electrocorticogram. All VPM cells (n = 8) responded vigorously to whisker movement even when the barrel cortex was profoundly depressed. In contrast, all POm cells (n = 9) failed to respond to whisker movement once the barrel cortex became depressed, typically about 25 minutes after the start of cortical cooling or magnesium application. POm cells regained responsiveness about 30 minutes after the cessation of cortical cooling or the washoff of magnesium. These findings indicate that the transmission of sensory information through the lemniscal pathway occurs independently of the state of cortex, whereas transmission through the paralemniscal pathway depends upon the state of the cortex itself.

Animals↗

Somatic sensory responses in the rostral sector of the posterior group (POm) and in the ventral posterior medial nucleus (VPM) of the rat thalamus.

The rodent barrel field cortex integrates somatosensory information from two separate thalamic nuclei, the ventral posterior medial nucleus (VPM) and the rostral sector of the posterior complex (POm). This paper compares the sensory responses of POm and VPM cells in urethane-anesthetized rats as a first step in determining how cortex integrates multiple sensory pathways. A complete representation of the contralateral body surface was identified in POm. Trigeminal receptive fields (RFs) of POm and VPM cells were mapped by computer-controlled displacement of individual whiskers; responses were quantified by using peristimulus time histograms. Average RF size was similar in POm (5.1 whiskers) and VPM (4.4 whiskers), but evoked responses in the two nuclei differed significantly according to all other measures. VPM cells were maximally responsive to one single whisker--the "center RF." Stimulating this whisker evoked, on average, a response of 1.4 spikes/stimulus at a latency of 7 ms; surrounding whiskers evoked responses of less than 1 spike/stimulus at latencies of greater than 8 ms. In contrast, POm cells were nearly equally responsive to several whiskers. Quantitative criteria allowed us to designate a single whisker as the "center RF" and stimulating this whisker evoked, on average, a response of 0.5 spikes/stimulus at a latency of 19 ms. VPM cells, but not POm cells, were able to "follow" repeated whisker deflection at greater than 5 Hz. We conclude that, when a single whisker is deflected, VPM activates the related cortical barrel-column at short latency--before the onset of activity in POm. The timing of activation could allow POm cells to modulate the spread of activity between cortical columns.

Animals↗

Demonstration of discrete place-defined columns--segregates--in the cat SI.

The SI forelimb area of cats was examined with receptive field (RF) mapping techniques. Arrays of closely spaced, near-radial microelectrode penetrations were inserted into the crown of postsigmoid gyrus of ketamine anesthetized subjects and minimal RFs were obtained at several depths. The minimal RF was defined as the skin site providing the strongest input to each recorded cluster of neurons. Data analysis showed that all studied cortical territories contained groups of discrete cortical columns, 300-400 microns in diameter. The columns were regarded as topographic entities because no change in minimal RF location could be observed within their boundaries. The boundaries of columns were sharp and could be unequivocally distinguished because the minimal RFs sampled on opposite sides of a boundary occupied displaced, nonoverlapping positions. Pair-wise comparison of single neuron maximal RFs (defined as the entire skin area providing input to the recorded neuron) further clarified the nature of the SI place-defined columns: (1) no systematic differences in maximal RF position could be demonstrated for different parts of the same column (even though the maximal RFs in most columns varied extensively in size and skin areas covered), and (2) at the boundary between neighboring columns maximal RFs shifted en masse to center on a new skin locus. These minimal and maximal RF observations strongly support our recent proposal that body surface is represented in SI by a honeycomblike mosaic of discrete place-defined cortical columns, segregates.

Animals↗

Similarity between the picornavirus VP3 capsid polypeptide and the Saccharomyces cerevisiae virus capsid polypeptide.

We have compared the sequence of the capsid polypeptide of the Saccharomyces cerevisiae double-stranded RNA virus, ScV, with those of the picornaviruses. A central region of 245 amino acids in the ScV capsid polypeptide of 680 amino acids has significant similarity to the picornavirus VP3. This similarity is more extensive than that already noted for the alphavirus capsid polypeptide and the picornavirus VP3 (Fuller, S.D. and Argos, P, EMBO J. 6, 1099, 1987). Together with the similarity between the ScV RNA polymerase and the picornavirus RNA polymerases, this result implies an evolutionary relationship between a simple double-stranded RNA virus of fungi and the small plus strand RNA animal viruses.

Amino Acid Sequence↗

Overlapping genes in a yeast double-stranded RNA virus.

The Saccharomyces cerevisiae viruses have a large viral double-stranded RNA which encodes the major viral capsid polypeptide. We have previously shown that this RNA (L1) also encodes a putative viral RNA-dependent RNA polymerase (D. F. Pietras, M. E. Diamond, and J. A. Bruenn, Nucleic Acids Res., 16:6226, 1988). The organization and expression of the viral genome is similar to that of the gag-pol region of the retroviruses. The complete sequence of L1 demonstrates two large open reading frames on the plus strand which overlap by 129 bases. The first is the gene for the capsid polypeptide, and the second is the gene for the putative RNA polymerase. One of the products of in vitro translation of the denatured viral double-stranded RNA is a polypeptide of the size expected of a capsid-polymerase fusion protein, resulting from a -1 frameshift within the overlapping region. A polypeptide of the size expected for a capsid-polymerase fusion product was found in virions, and it was recognized in Western blots (immunoblots) by antibodies to a synthetic peptide derived from the predicted polymerase sequence.

Base Sequence↗

Evidence for a mosaic representation of the body surface in area 3b of the somatic cortex of cat.

A discontinuous representation of the forelimb body surface in area 3b is proposed. Two different methods were used: single-neuron receptive-field (RF) mapping in unanesthetized cats (maximal RF) and multiunit RF mapping in deeply anesthetized cats (minimal RF). Ten or more maximal RFs were sampled in each of 14 near-radial microelectrode penetrations. In 6 penetrations, the maximal RFs of all sampled neurons (despite prominent variations in RF size and shape) shared in common a small skin area--termed the "RF center." Each of the remaining penetrations had to be divided into at least two segments (6 penetrations) or three segments (2 penetrations), for all maximal RFs mapped in a segment to include a common skin site. In six penetrations, after maximal RFs were mapped, deep general anesthesia was induced and minimal RFs were mapped in the same penetration at cortical sites separated by 150 microns. Minimal RFs closely matched the RF centers defined by maximal RFs in the same penetration. In penetrations that mapped two or three RF centers, a rapid transition in minimal RF position was detected at the same cortical site where the shift in RF center was detected. Closely spaced penetrations revealed discrete cortical columns, having the size and shape of 350- to 400-microns-diameter irregular hexagons, such that the identical minimal RF was mapped at any site within a column. The forelimb body surface in cat 3b thus appears to be represented by a mosaic of discrete columns--an organization similar to the whisker representation in rodent primary somatosensory cortex.

Animals↗

Mitogen responses and interferon production after exposure of human macrophages to infectious and inactivated influenza viruses.

Human macrophages were exposed to two influenza A viruses representing different subtypes. The donors were likely to have been exposed to one subtype (H3N2) but not to the other (H0N 1). Similar effects upon the macrophages were observed for both subtypes: macrophage enhancement of mitogen-stimulated lymphocyte transformation responses was depressed, and the macrophages produced interferon. In contrast, macrophages exposed to inactivated virus exhibited normal enhancement of lymphocyte transformation response, yet produced interferon, although in lower titers than did macrophages exposed to infectious virus.

Hot Temperature↗