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Biomedical subjects

L M Kay

Publications and source records attributed to L M Kay.

9 recordsLinked to original sources
PubMed1999

Odor- and context-dependent modulation of mitral cell activity in behaving rats.

The projections and odor responses of mammalian olfactory receptor neurons, as well as the physiology of the bulb's principal neurons-the mitral cells (MCs)-are known from studies in slices and anesthetized animals. In behaving rats trained to discriminate between two odors associated with different reinforcers, we examined MC responses following alternated odor-reinforcer pairings. Whereas only 11% of the recorded MCs showed changes in odor-selective firing rate during the odor-sampling phase, 94% of MCs modulated activity during specific behaviors surrounding odor sampling. These cell- and odor-selective responses were not primary sensory responses; rather, they depended (reversibly) on the predictive value of each odor. MC activity thus depends critically on efferent influences linked to the animal's experience and behavior.

Animals↗
PubMed1998

Bidirectional processing in the olfactory-limbic axis during olfactory behavior.

Field potentials were recorded simultaneously from the olfactory bulb (OB), prepyriform cortex (PPC), entorhinal cortex (EC), and dentate gyrus (DG) of rats trained to respond to appetitively reinforced odors. Preafferent anticipatory events in the beta band (12-35 Hz) suggest transmission from EC to OB before the odorant stimulus. Gamma band (35-120 Hz) power in olfactory regions is significantly reduced during stimulus presentation as compared with high values during preafferent expectation. High coherence of OB and PPC gamma activity during the preodorant control period is interrupted before the stimulus and is followed by increased gamma coherence among OB, EC, and DG. These results suggest that olfactory perceptual processing is bidirectional and covers a wide frequency range.

Afferent Pathways↗
PubMed1996

Reafference and attractors in the olfactory system during odor recognition.

Olfactory bulb activity has been postulated to be chaotic, as measured in the EEG, and to be subject to an attractor with many "wings" enabling classification of different learned odor classes. Two parallel questions are thus addressed by the work presented here: (1) what is the evidence for attractors in the olfactory system, which can mediate learned odor classes? and (2) how does the olfactory system enter a specific attractor or attractor wing associated with the learned odor during the classification process? Both of these questions address the wider notion of endogenous activity preparing the system for an expected stimulus, which is at the basis of the reafference principle. By viewing the brain as a distributed complex dynamical system with global attractors, these questions can be answered together. Rats were implanted with bipolar macroelectrodes in the Olfactory Bulb (OB), Prepyriform Cortex (PPC), Entorhinal Cortex (EC), and Dentate Gyrus (DG), and then trained in an operant paradigm to press a bar for a reward in the presence of one odor and to receive no reward in the presence of another odor. Local Field Potentials (LFP) were recorded simultaneously from the structures during the operant task. We present evidence for three endogenous events: (1) preafference, which is manifested both by the EC entering an attractor and a mid-range signal (15-30 Hz) which appears to be passed from the EC to the OB just before the OB enters an attractor; (2) afference, where the OB enters an attractor during the odor recognition period of the experiment and the LFP recordings indicate that the OB drives the other structures in all frequency bands, especially the high gamma band (65-100 Hz) associated with the OB burst frequency; and (3) reafference or post-afference, which is accompanied by a lower frequency gamma band signal (40-60 Hz) originating in the PPC and passed to both the OB and the EC just before the onset of the motor response to the odor. We use a new method, NECTAR (Nonparametric Exact Contingency Table Association Routine), related to mutual information, to verify what is seen with coherence and phase estimates, the apparent driving of each structure at different times in the odor trials, and to display evidence for non-periodic attractors governing both individual physiological structures and the system of structures. This is the first evidence of an endogenous, limbic event associated with sensory perceptual tuning in a mammal. These results are also the first experimental confirmation that the attractors governing olfactory activity involve multiple sites in the olfactory/limbic system and implement the process of attention.

Adaptation, Physiological↗
PubMed1989

Beta-cluster haplotypes, alpha-gene status, and hematological data from SS, SC, and S-beta-thalassemia patients in southern California.

The beta-gene-cluster haplotype and alpha-gene status were determined for 221 patients with sickle cell anemia, 41 with SC disease, and 21 with S-beta-thalassemia. Among SS patients, eleven beta S haplotypes were found in 21 combinations. Three haplotypes--the Benin (Ben) [---+-], the Central African Republic (CAR) [+---+], and the Senegal (Sen) [+- ]--comprise 61%, 21%, and 10% of the chromosomes, respectively. Cleavage at the Xmn I site 5' to the G gamma gene was observed only when the Senegalese arrangement was present. The linear correlation which exists between the absolute value of the G gamma chains and the Hb F for each haplotype combination suggests a feed-back mechanism which controls the G gamma to A gamma ratio and thus the Hb F level (or vice versa). The A gamma T chain was present with specific haplotypes [++-++] and [++-+-]. Heterozygous or homozygous alpha-thalassemia-2 was present in 36% of the SS patients and was randomly distributed among beta S-gene-cluster haplotypes. The variable levels of hemoglobin, MCV, Hb F, G gamma chains, and Hb A2 are in response to the heterogeneous genetic mix of the beta S-gene-cluster haplotypes and alpha-thalassemia-2 in American patients with sickle cell anemia. The influence of alpha-thalassemia-2 on the level of Hb F is dependent on the beta S-cluster haplotype. Hb A2 levels increased with decrease in the number of alpha genes. Among SC and S-beta-thalassemia patients the beta-cluster polymorphisms on the beta S chromosome were those commonly associated with the African origins of beta S haplotype. The haplotype [+--+-] was present on the C chromosome in 90% of the cases. Most beta-thalassemia chromosomes had haplotypes that matched the common African polymorphisms. An alpha-gene deletion was found in 29% of the SC and S-beta-thalassemia patients.

Adolescent↗
PubMed1981

The imbalance of chain synthesis in hemoglobin F.

The synthesis of Hb F has been found to be unbalanced in a number of conditions, including homozygous HPFH, sickle-cell anemia, and normal term cord bloods. In this study, the counts from the pre-gamma and pre-alpha zones of the chain separation chromatogram are considered to be modified gamma and alpha chains, respectively, and are included in calculating the gamm/alpha ratios for cord blood and sickle-cell blood. The gamma chain is labeled about 52% as efficiently as the alpha chain in reticulocytes. It is possible that nu chain synthesis is balanced in the bone marrow, but subsequently becomes unbalanced in the reticulocyte.

Anemia, Sickle Cell↗
PubMed1977

Structure of bovine trypsinogen at 1.9 A resolution.

The three-dimensional crystal structure of bovine trypsinogen at approximately pH 7.5 was initially solved at 2.6 A resolution using the multiple isomorphous replacement method. Preliminary refinement cycles of the atomic coordinates trypsinogen have been carried out first to a resolution of 2.1 A, and later to 1.9 A, using constrained difference Fourier refinement; During the process, structure factors Fc and phi c were calculated from the trypsinogen structure and final interpretation was based on an electron-density map computed with terms (2 Fo - Fc) and phases phic at a resolution of 1.9 A. Crystals of trypsinogen grown from ethanol-water mixtures are trigonal with space group P3121, and cell dimension a = 55.17 A and c = 109.25 A. The structure is compared with the bovine diisopropylphosphoryltrypsin structure at approximately pH 7.2, oirginally determined from orthohombic crystals by Stroud et al. (Stroud, R.M., Kay L.M., and Dickerson, R.E. (1971), Cold Spring Harbor Symp. Quant. Biol. 36, 125-140; Stroud, R.M., Kay, L.M., and Dickerson, R.E. (1974), J. Mol. Biol. 83, 185-208), and later refined at 1.5 A resolution by Chambers and Stroud (Chambers, J.L., and Stroud, R.M. (1976), Acta Crystallogr. (in press)). At lower pH, 4.0-5.5 diogen, with cell dimensions a = 55.05 A and c = 109.45 A. This finding was used in the solution of the six trypsinogen heavy-atom derivatives prior to isomorphous phase analysis, and as a further basis of comparison between trypsinogen and the low pH trypsin structure. There are small differences between the two diisopropylphosphoryltrypsin structures. Bovine trypsinogen has a large and accessible cavity at the site where the native enzyme binds specific side chains of a substrate. The conformation and stability of the binding site differ from that found in trypsin at approximately pH 7.5, and from that in the low pH form of diisopropylphosphoryltrypsin. The catalytic site containing Asp-102, His-57, and Ser-195 is similar to that found in trypsin and contains a similar hydrogen-bounded network. The carboxyl group of Asp-194, which is salt bridged to the amino terminal of Ile-16 in native trypsin or other serine proteases, is apparently hydrogen bonded to internal solvent molecules in a loosely organized part of the zymogen structure. The unusually charged N-terminal hexapeptide of trypsinogen, whose removal leads to activation of the zymogen, lies on the outside surface of the molecule. There are significant structural changes which accompany activation in neighboring regions, which include residues 142-152, 215-550, 188A-195. The NH group of Gly-193, normally involved in stabilization of reaction intermediates (Steitz, T.A., Henderson, R., and Blow, D.M. (1969), J. Mol. Biol. 46, 337-348; Henderson, R. (1970), J. Mol. Biol. 54, 341-354; robertus, J.D., Kraut, J., Alden, R.A., and Birkoft, J.J. (1972), Biochemistry 11, 4293-4303) in the enzyme, is moved 1.9 A away from its position in trypsin...

Animals↗