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Biomedical subjects

L B Cohen

Publications and source records attributed to L B Cohen.

At least 19 recordsLinked to original sources

Representation of odorants by receptor neuron input to the mouse olfactory bulb.

To visualize odorant representations by receptor neuron input to the mouse olfactory bulb, we loaded receptor neurons with calcium-sensitive dye and imaged odorant-evoked responses from their axon terminals. Fluorescence increases reflected activation of receptor neuron populations converging onto individual glomeruli. We report several findings. First, five glomeruli were identifiable across animals based on their location and odorant responsiveness; all five showed complex response specificities. Second, maps of input were chemotopically organized at near-threshold concentrations but, at moderate concentrations, involved many widely distributed glomeruli. Third, the dynamic range of input to a glomerulus was greater than that reported for individual receptor neurons. Finally, odorant activation slopes could differ across glomeruli, and for different odorants activating the same glomerulus. These results imply a high degree of complexity in odorant representations at the level of olfactory bulb input.

Acetates↗

Infant object segregation implies information integration.

Researchers, including Needham (2001, this issue), have found that infants as young as 4.5 months of age have the ability to use featural information to segregate objects. However, considerable research on infants' perception of color, shape, size, orientation, and so on has shown that infants younger than 4.5 months are capable of using these featural cues to discriminate between objects or other test items. Infants as young as 2 months of age also can perceive a moving object as unified. In this article, we argue for an information processing explanation of these results, which centers on the development of infants' ability to integrate both featural and object information. The proposed explanation is based upon L. B. Cohen's (1991, 1998) information processing propositions and is consistent with the evidence on object segregation as well as evidence from our laboratory and others' on infant perception and cognition.

Child Development↗

Acute eosinophilic pneumonia in AIDS.

A 39-year-old man with AIDS presented with acute respiratory distress and diffuse bilateral infiltrates seen on a chest radiograph. Acute eosinophilic pneumonia (AEP) was diagnosed by thoracoscopic lung biopsy. There was no evidence of an infectious etiology, and the patient rapidly improved with corticosteroid therapy. Several of the idiopathic interstitial pneumonias have been reported in adult patients with AIDS. To our knowledge, this case represents the first tissue-confirmed case of AEP associated with adult AIDS.

Acquired Immunodeficiency Syndrome↗

Distributed and partially separate pools of neurons are correlated with two different components of the gill-withdrawal reflex in Aplysia.

We compared the spike activity of individual neurons in the Aplysia abdominal ganglion with the movement of the gill during the gill-withdrawal reflex. We discriminated four populations that collectively encompass approximately half of the active neurons in the ganglion: (1) second-order sensory neurons that respond to the onset and offset of stimulation of the gill and are active before the movement starts; (2) neurons whose activity is correlated with the position of the gill and typically have a tonic output during gill withdrawal; (3) neurons whose activity is correlated with the velocity of the movement and typically fire in a phasic manner; and (4) neurons whose activity is correlated with both position and velocity. A reliable prediction of the position of the gill is achieved only with the combined output of 15-20 neurons, whereas a reliable prediction of the velocity depends on the combined output of 40 or more cells.

Action Potentials↗

Odors elicit three different oscillations in the turtle olfactory bulb.

We measured the spatiotemporal aspects of the odor-induced population response in the turtle olfactory bulb using a voltage-sensitive dye, RH414, and a 464-element photodiode array. In contrast with previous studies of population activity using local field potential recordings, we distinguished four signals in the response. The one called DC covered almost the entire area of the olfactory bulb; in addition, three oscillations, named rostral, middle, and caudal according to their locations, occurred over broad regions of the bulb. In a typical odor-induced response, the DC signal appeared almost immediately after the start of the stimulus, followed by the middle oscillation, the rostral oscillation, and last, the caudal oscillation. The initial frequencies of the three oscillations were 14.1, 13.0, and 6.6 Hz, respectively. When the rostral and caudal oscillations occurred together, their frequencies differed by a factor of 1.99 +/- 0.01. The following evidence suggests that the four signals are functionally independent: (1) in different animals some signals could be easily detected whereas others were undetectable; (2) the four signals had different latencies and frequencies; (3) the signals occurred in different locations and propagated in different directions; (4) the signals responded differently to changes in odor concentration; (5) the signals had different shapes; and (6) the rostral and caudal signals added in a simple, linear manner in regions where the location of the two signals overlapped. However, the finding that the frequency of the rostral oscillation is precisely two times that of the caudal oscillation suggests a significant relationship between the two. The location of the caudal oscillation in the bulb changed from cycle to cycle, implying that different groups of neurons are active in different cycles. This result is consistent with the earlier findings in the olfactory system of the locust (). Our results suggest an additional complexity of parallel processing of olfactory input by multiple functional population domains.

Animals↗

Imaging membrane potential with voltage-sensitive dyes.

Membrane potential can be measured optically using a variety of molecular probes. These measurements can be useful in studying function at the level of an individual cell, for determining how groups of neurons generate a behavior, and for studying the correlated behavior of populations of neurons. Examples of the three kinds of measurements are presented. The signals obtained from these measurements are generally small. Methodological considerations necessary to optimize the resulting signal-to-noise ratio are discussed.

Animals↗

Infants' association of linguistic labels with causal actions.

Six experiments examined infants' ability to associate nonsense words with 2 causal actions: pushing and pulling. Although Experiment 1 found that 14-month-olds failed to form word-action associations, 18-month-olds in Experiment 2 provided reliable evidence of doing so. Additional experiments explored why 14-month-olds may not have formed such an association. Experiment 3 examined 14-month-olds' ability to discriminate a change in either the action or the label when the other element was held constant. Infants discriminated the change in label but not the change in action. When the language labels were replaced with music (Experiments 4-6), 14-month-old infants responded in terms of and discriminated between pushing and pulling. These results, in comparison with those from Experiments 1 and 3, suggest that for 14 month-olds, attempting to associate labels with actions may interfere with their discrimination of similar actions.

Age Factors↗

Presynaptic inhibition of primary olfactory afferents mediated by different mechanisms in lobster and turtle.

Presynaptic regulation of transmission at the first olfactory synapse was investigated by selectively imaging axon terminals of receptor neurons in the lobster olfactory lobe and turtle olfactory bulb. In both species, action potential propagation into axon terminals after olfactory nerve stimulation was measured using voltage-sensitive dyes. In addition, in the turtle, calcium influx into terminals was measured by selectively labeling receptor neurons with dextran-conjugated calcium indicator dyes. In the lobster, application of the inhibitory transmitters GABA or histamine suppressed action potentials in the terminals. The suppression was blocked by picrotoxin and cimetidine, respective antagonists to lobster GABA and histamine receptors. These results suggest that previously characterized GABA and histaminergic interneurons regulate olfactory input by suppressing action potential propagation into axon terminals of olfactory afferents. In contrast, in the turtle olfactory bulb, neither GABA nor dopamine had any effect on receptor cell action potentials as measured with voltage-sensitive dyes. However, calcium influx into axon terminals was reduced by the GABA(B) agonist baclofen and the dopamine D(2) agonist quinpirole, and paired-pulse suppression of calcium influx was reduced by the GABA(B) antagonist saclofen. These results indicate that in the turtle, GABA and dopamine mediate presynaptic inhibition not by affecting action potentials directly, as in the lobster, but by reducing calcium influx via GABA(B) and dopamine D(2) receptors. Thus, although mediated by different cellular mechanisms, presynaptic regulation of olfactory input to the CNS, via dual synaptic pathways, is a feature common to vertebrates and invertebrates. This inhibition may be important in the processing of olfactory information.

Animals↗

Thalidomide therapy for patients with refractory Crohn's disease: an open-label trial.

BACKGROUND & AIMS: Inhibition of tumor necrosis factor is a proposed mechanism for the anti-inflammatory properties of thalidomide. We performed an open-label trial of thalidomide in refractory Crohn's disease. METHODS: Twenty-two patients with refractory Crohn's disease (Crohn's Disease Activity Index [CDAI] > 200 and/or draining perianal disease) initiated therapy with thalidomide, 200 mg at bedtime (18 patients), or 300 mg at bedtime (4 patients). CDAI and goal interval scores (GIS) were assessed at weeks 0, 4, and 12. Clinical response for patients with luminal disease was defined as reduction in CDAI score of >150 points and for fistula patients was 2 scores of >/=1+ in 3 parameters of the GIS. Clinical remission was defined as a total CDAI < 150 (luminal patients) or >/=2+ for all parameters of the GIS (fistula patients). RESULTS: Nine patients with luminal disease and 13 with fistulas (16 male, 6 female) were enrolled. The median CDAI score at entry was 371 (95-468). Sixteen patients completed 4 weeks of treatment (12 clinical responses, 4 clinical remissions). All 14 patients completing 12 weeks met criteria for clinical response. Nine achieved clinical remission (3 luminal, 6 fistula patients). The median CDAI score was 175 (30-468; P < 0.001 vs. baseline). CONCLUSIONS: Thalidomide is efficacious in some patients with refractory Crohn's disease.

Adult↗

Voltage-sensitive dyes for monitoring multineuronal activity in the intact central nervous system.

Optical monitoring of activity provides new kinds of information about brain function. Two examples are discussed in this article. First, the spike activity of many individual neurons in small ganglia can be determined. Second, the spatiotemporal characteristics of coherent activity in the brain can be directly measured. This article discusses both general characteristics of optical measurements (sources of noise) as well as more methodological aspects related to voltage-sensitive dye measurements from the nervous system.

Action Potentials↗

Acquisition of word-object associations by 14-month-old infants.

The following experiments were designed to determine the age at which infants can first readily learn word--object pairings with only minimal exposure and without social or contextual support. To address this question, 8- to 14-month-old infants were tested on their ability to form word--object associations in a "switch" design. Infants were habituated to 2 word--object pairings and then tested with 1 trial that maintained a familiar word--object pairing and 1 that involved a familiar word and object in a new combination. Across 6 experiments, only 14-month-old infants formed word--object associations under these controlled testing conditions but appeared to do so only when the objects were moving. Although 8- to 12-month-olds did not form the associations, they appeared to process both the word and the object information. These studies provide strong evidence that 14-month-old infants can rapidly learn arbitrary associations between words and objects, that this ability appears to develop at about 14 months of age, and that the Switch design is a useful method for assessing word--object learning in infancy.

Age Factors↗

Presynaptic afferent inhibition of lobster olfactory receptor cells: reduced action-potential propagation into axon terminals.

Action-potential propagation into the axon terminals of olfactory receptor cells was measured with the use of voltage-sensitive dye imaging in the isolated spiny lobster brain. Conditioning shocks to the olfactory nerve, known to cause long-lasting suppression of olfactory lobe neurons, allowed the selective imaging of activity in receptor cell axon terminals. In normal saline the optical signal from axon terminals evoked by a test stimulus was brief (40 ms) and small in amplitude. In the presence of low-Ca2+/high-Mg2+ saline designed to reduce synaptic transmission, the test response was unchanged in time course but increased significantly in amplitude (57 +/- 16%, means +/- SE). This increase suggests that propagation into receptor cell axon terminals is normally suppressed after a conditioning shock; this suppression is presumably synaptically mediated. Thus our results show that presynaptic inhibition occurs at the first synapse in the olfactory pathway and that the inhibition is mediated, at least in part, via suppression of action-potential propagation into the presynaptic terminal.

Action Potentials↗

Morphodynamics and pathology of blood vessels III--comparative morphologic study of contraction of smooth muscle cells of hollow viscera and its application to vasoconstriction and vasospasm.

The morphologic changes in the walls of hollow viscera caused by contraction and relaxation of smooth muscle cells were studied from autopsy and surgical specimens. The specimens studied included: esophageal spasm (corkscrew and nutcracker esophagus), contraction of the lower esophageal sphincter with marked esophageal dilatation, gaseous distension of the stomach, contraction of the gastric pylorus, bladder and anal sphincter, physiological segmental constriction of the small and large intestines, constriction and distension of the gallbladder, urinary bladder and bronchi, and postpartum contraction of the uterus. In contrast to distension, the constriction of hollow viscera shows marked reduction of the external circumference and diameter with thickening of the wall, contraction of smooth muscle cells, thickening of muscle bundles, remodeling of wall structure, and narrowing or obliteration of the lumen. Morphologic evidence of contraction of smooth muscle cells is demonstrated by varying degrees of typical lengthwise shortening of the cells and squeezing and folding of the nuclei depending on the degree of cytoplasmic contraction of the smooth muscle cells. Using these same classic morphologic signs, we have attempted to study constriction and distension of arteries and arterioles. We can demonstrate contraction of smooth muscle cells and remodeling of arterial and arteriolar walls in patients with spastic coronary artery thrombosis, cocaine-induced coronary artery thrombosis, acute constriction of mesenteric arteries with lacerations of arterial wall, and dissecting hemorrhages induced by large doses of intravenous infusion of vasoconstrictors for hemorrhagic shock, and in patients with sustained, accelerated, or malignant hypertension.

Adult↗

Visual stimuli induce waves of electrical activity in turtle cortex.

The computations involved in the processing of a visual scene invariably involve the interactions among neurons throughout all of visual cortex. One hypothesis is that the timing of neuronal activity, as well as the amplitude of activity, provides a means to encode features of objects. The experimental data from studies on cat [Gray, C. M., Konig, P., Engel, A. K. & Singer, W. (1989) Nature (London) 338, 334-337] support a view in which only synchronous (no phase lags) activity carries information about the visual scene. In contrast, theoretical studies suggest, on the one hand, the utility of multiple phases within a population of neurons as a means to encode independent visual features and, on the other hand, the likely existence of timing differences solely on the basis of network dynamics. Here we use widefield imaging in conjunction with voltage-sensitive dyes to record electrical activity from the virtually intact, unanesthetized turtle brain. Our data consist of single-trial measurements. We analyze our data in the frequency domain to isolate coherent events that lie in different frequency bands. Low frequency oscillations (<5 Hz) are seen in both ongoing activity and activity induced by visual stimuli. These oscillations propagate parallel to the afferent input. Higher frequency activity, with spectral peaks near 10 and 20 Hz, is seen solely in response to stimulation. This activity consists of plane waves and spiral-like waves, as well as more complex patterns. The plane waves have an average phase gradient of approximately pi/2 radians/mm and propagate orthogonally to the low frequency waves. Our results show that large-scale differences in neuronal timing are present and persistent during visual processing.

Animals↗

Functions of the LE sensory neurons in Aplysia.

Mechanosensory neurons which innervate the siphon and have their cell bodies in the LE cluster of the abdominal ganglion of Aplysia have revealed many cellular and molecular processes that may play general roles in learning and memory. It was initially suggested that these cells are largely responsible for triggering the gill-withdrawal reflex evoked by weak siphon stimulation, and that most of this effect is mediated by their monosynaptic connections to gill motor neurons. This implied a simple link between plasticity at these synapses and modifications of the reflex during learning. We review more recent studies from several laboratories showing that the LE cells are not activated by very weak tactile stimuli that elicit the gill-withdrawal reflex, and that an unidentified population of siphon sensory neurons has lower mechanosensory thresholds and produces shorter latency responses. Furthermore, the direct connections between LE cells and gill motor neurons make a minor contribution when the reflex is elicited in pinned siphon preparations by light stimuli that weakly activate the LE cells. Because weak mechanical stimulation of the unrestrained siphon causes little or no LE cell activation, it is unlikely that, under natural conditions, sensitization or conditioning of reflex responses elicited by light siphon touch depends upon plasticity of LE cell synapses onto either motor or interneurons. The LE cells appear to function as nociceptors because they are tuned to noxious stimuli and, like mammalian nociceptors, show peripheral sensitization following nociceptive activation. This sensitization and the profound activity-dependent potentiation of LE synapses indicate that LE cell contributions to defensive reflexes should be largest during and after intense activation of the LE cells by noxious stimulation (with the LE cell plasticity contributing to long-lasting memory of peripheral injury). The LE sensory neurons offer special opportunities for direct tests of this and other hypotheses about specific mnemonic functions of fundamental mechanisms of neural plasticity.

Animals↗