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B N Baker

Publications and source records attributed to B N Baker.

At least 19 recordsLinked to original sources

Acoustic chiasm V: inhibition and excitation in the ipsilateral and contralateral projections of LSO.

When this series of experiments was begun in 1984, the activity of each lateral superior olive (LSO) in the mammalian hindbrain was known to encode the hemifield of acoustic space containing a sound source. However, the almost random bilaterality of its ascending projections seemed to jumble that identification before reaching the midbrain. At the same time, electrophysiological studies of LSO and its efferent target in the inferior colliculus, along with the strictly contralateral deficits in sound localization resulting from unilateral lesions above the level of the superior olives, indicated that hemifield allegiance was largely maintained (though reversed) at the midbrain. Here we present seven lines of biochemical evidence, some combined with prior ablations, supporting the notion that the anatomical segregation of the ipsilateral and contralateral fibers ascending from the LSO is accompanied by a corresponding segregation of their neurotransmitters: most of the ascending ipsilateral projection is probably glycinergic and, hence, inhibitory in effect, while most of the contralateral projection is probably glutamatergic/aspartergic and, hence, excitatory in effect. Taken together, the inhibitory ipsilateral projections and the excitatory contralateral projections serve to amplify functional contralaterality at the higher levels of the auditory system.

Acoustic Stimulation

Acoustic chiasm. III: Nature, distribution, and sources of afferents to the lateral superior olive in the cat.

The outcomes of seven experiments are reported, each directed to the nature and sources of the excitation and inhibition impinging on the lateral superior olive (LSO) in cats. In the first experiment, we used conventional 14C 2-DG methods to determine the specificity, precision, and extent of symmetry in the stimulation reaching LSO from the ipsilateral and contralateral ears. In Experiment 2, we sought the presence of GABA and glycine receptors in LSO using conventional, in vitro receptor-binding methods. On the basis of these results, we used in vitro high-affinity uptake methods in Experiment 3 to seek evidence that some of the terminals as well as the receptors in LSO are glycinergic. In Experiment 4, we used immunocytochemical methods to show that the somata known to supply the contralateral projections to LSO, and their terminals in LSO, are each immunoreactive with an antibody directed to a glycine-protein conjugate. In Experiment 5, we made use of a glycinergic neuron's avidity for transporting glycine retrogradely to label the likely sources of the glycinergic terminals in LSO. In Experiment 6, we used immunocytochemical methods to show that the spherical and globular cells of the ventral cochlear nucleus and terminals in LSO and in MTB are glutamatergic and/or aspartergic. In Experiment 7, we used receptor binding methods to determine whether the glutamate/aspartate receptors in LSO are probably of the kainate or of the quisqualate type. The results of the several experiments suggest that probably glutamate-quisqualate synapses mediate LSO's ipsilaterally driven excitatory responses and glycinergic synapses mediate its contralaterally driven inhibitory responses. The two types of input appear to be well matched in LSO's medial and middle limbs with glycinergic terminals mostly perisomatic and glutamatergic terminals mostly peridendritic. However, LSO's low frequency lateral limb appears to be somewhat different; it receives less stimulation from the contralateral ear. Instead, LSO's lateral limb may receive some of its glycinergic input directly from the ipsilateral ventral cochlear nucleus and/or indirectly via the juxtaposed lateral nucleus of the trapezoid body.

Afferent Pathways

Neuroanatomical distribution of receptors for three potential inhibitory neurotransmitters in the brainstem auditory nuclei of the cat.

In order to visualize the relative abundance of each of three potentially inhibitory neurotransmitters in the nuclei of the brainstem auditory pathway, receptor sites for glycine, GABA-A, and muscarinic acetylcholine (ACh) have been localized in the cat's brainstem auditory system. Conventional autoradiographic receptor-binding procedures were used and the distributions of the receptors were inferred from the respective distributions of tritiated strychnine, muscimol, and quinuclidinyl benzilate (QNB) binding sites. The results show that glycine may be the major inhibitory neurotransmitter in the auditory system as it ascends to the midbrain in that relatively high levels of strychnine binding are present in every major nucleus of the system. In contrast, high levels of muscimol binding of high-affinity GABA-A receptors are confined mostly to the dorsal cochlear nucleus, the dorsal nucleus of the lateral lemniscus, and the central and cortical regions of the inferior colliculus, while high levels of QNB binding of muscarinic ACh receptors are seen only in the central and cortical regions of the inferior colliculus.

Animals

"Self-screening" of rhodopsin in rod outer segments.

Microspectrophotometry (MSP) shows rhodopsin highly concentrated (about 3.0 mmol/l) in rod outer segments (ROS). Calculation of the in vivo absorption spectrum of human rhodopsin from such data reveals a striking failure to agree with the action spectrum of human rod vision. Agreement is good between the spectral distribution of absorption coefficients and the action spectrum, but the "concentration-broadening" (or "self-screening") introduced by the high end on absorbance at this concentration results in a misfit among the largest in the 93 years comparisons of this kind have been made! To deal with this anomaly, it has been suggested that "concentration-broadening" is inappropriate for rhodopsin in rod vision. This proposal was tested by comparing rod action spectra of 15-day-old and adult rats, since the lengths of ROS increase by a factor of about two in maturation. Three lines of evidence are inconsistent with it. Although the conundrum remains unexplained, it cannot be dismissed by supposing "self-screening" inappropriate for night vision.

Aging

Progression and reversibility of early light-induced alterations in rat retinal rods.

The temporal sequence of ultrastructural changes induced in the rat rod photoreceptor by 80 lux light-stress has been studied. The changes seen were compared with those produced by a much dimmer (3 lux) illumination. Some of the early signs of abnormality were (1) degradation of some disk membranes at the tips of outer segments, (2) disaggregation and detachment of ribosomes, (3) lighter matrices in swollen mitochondria, (4) disappearance of the Golgi apparatus, (5) proliferation of autophagic bodies in the inner segments, and (6) appearance of perimitochondrial membrane whorls in the synaptic terminals. No single change could be identified that would inexorably lead to cell death. The overall picture, however, suggested that an inability of the cell to maintain its anabolic balance is responsible for the pyknosis that occurs when the 80 lux exposure exceeds 12-15 h. All changes were reversible when exposure duration did not exceed 12 h, the normal length of the light cycle for these rats.

Animals

Alteration of disk-shedding patterns by light-onset of higher than normal intensity.

Rod outer segment (ROS) disk-shedding patterns were determined in the albino rat eye. All of the animals had the same, low-intensity-light histories, but on the day that shedding patterns were to be measured the rats were divided into three groups: one which did not have any lights turned on at 0700 hr ('contained dark' group); one which had normal, 3-lx light turned on ('colony' group); one which had a brighter-than-normal light turned on ('80-lx' group). The 'continued dark' group displayed a broad profile of shedding over time which persisted because phagosomes disappeared so slowly. The 'colony' group showed the same initial rate of phagosome production as did the 'continued dark' group but a much accelerated rate of phagosome disappearance. The '80-lx' group showed no rate of phagosome production; rather there was a simple, rapid exponential disappearance of those phagosomes which existed just prior to light onset. The kinetics of these phenomena are described in a model, rate constants for which were obtained from our data and simulated on an analog computer. The analysis of the three shedding patterns indicates the existence of an intensity-dependent disappearance rate and suggests an inhibition of shedding and/or phagocytosis by intensity greater than that of the usual environment.

Animals

Oil droplets of the retinal epithelium of the rat.

Oil droplets are observed in the retinal pigment epithelium (RPE) of both light- and dark-adapted rats. The accumulation of these droplets is strongly correlated with the clearance of large phagosomes that are found on a circadian basis in the RPE. Although strongly correlated with phagosomes in this way, the composition of the oil droplets does not resemble the lipid composition of rod outer segments (ROS). The important differences are that most of the 18:0 fatty acid (stearic) and virtually all of the polyunsaturated ones (principally docosahexaenoic, 22:6) are absent from the droplets. The major (greater than 95%) constituents of the droplets are triglycerides admixed with small amounts of vitamin A esters (less than 5%). This result suggests that certain of the ROS lipids, especially the polyunsaturated fatty acids, are cleared quickly from the RPE and are, perhaps, recycled to the neural retina. Such a process would account for the known ability of the retina to conserve the polyunsaturates despite dietary deficiencies.

Adaptation, Ocular

Retinal light-damage in albino rats: lysosomal enzymes, rhodopsin, and age.

The damaging effects incurred during a light-insult on the albino rat retina are studied separately from the resultant loss of visual cells which occurs. Groups of rats, 5-20 weeks of age, are exposed to 48 hr of 80 lux illumination, maintained in the dark for various lengths of time, and then killed. Beginning at light-off and continuing throughout 3 days of darkness, assays are made of (i) outer nuclear layer thickness; (ii) whole retina rhodopsin levels; and (iii) activities of lysosomal proteases known to be important in the degradation of retinal and ocular tissue. It is found that (a) having been given the light-insult, most of the visual cells that will die and disappear do so during the dark, postexposure period; (b) the retinas of all the animals show a limited capability for regenerating rhodopsin after the light-insult but younger animals are somewhat more successful at sustaining this than are older ones; (c) proteolytic enzyme activity is greatest in older animals which are also the ones that lose the most cells.

Aging

Evidence for conformeric states of rhodopsin.

Spectrophotometric measurements of metarhodopsin II appearance are made on five different kinds of rhodopsin preparations. Although the preparations differ greatly in their rhodopsin: phospholipid ratio, the meta II kinetics in all of them are strikingly similar in certain respects. Meta II appearance kinetics in all of the preparations are best described by two and only two exponentials. The ratio of these two rates is always about 5. The fast fraction: slow fraction ratio depends upon temperature. These fractions are reversibly convertible in the dark, and are interconverted on a time-scale which is long compared to the meta II appearance rate. It is shown that the kinetics of the earlier step in the bleaching sequence, viz., lumi-leads to meta I, is also described by double exponentials. Again the ratio of rates is ca. 5 and the fast-slow fractions correspond to those found in the meta I leads to meta II step. It is proposed that these facts support an hypothesis for the existence of two conformeric states of rhodopsin which are in thermal equilibrium. Thermodynamic parameters associated with this proposed equilibrium are presented.

Protein Conformation

Visual sensitivity.

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Adaptation, Ocular