The Rapid Cognitive Screen (RCS): A Point-of-Care Screening for Dementia and Mild Cognitive Impairment.

OBJECTIVES: There is a need for a rapid screening test for mild cognitive impairment (MCI) and dementia to be used by primary care physicians. The Rapid Cognitive Screen (RCS) is a brief screening tool (< 3 min) for cognitive dysfunction. RCS includes 3-items from the Veterans Affairs Saint Louis University Mental Status (SLUMS) exam: recall, clock drawing, and insight. Study objectives were to: 1) examine the RCS sensitivity and specificity for MCI and dementia, 2) evaluate the RCS predictive validity for nursing home placement and mortality, and 3) compare the RCS to the clock drawing test (CDT) plus recall. METHODS: Patients were recruited from the St. Louis, MO Geriatric Research Education and Clinical Center (GRECC), Veterans Affairs Medical Center (VAMC) hospitals (study 1) or the Saint Louis University Geriatric Medicine and Psychiatry outpatient clinics (study 2). Study 1 participants (N=702; ages 65-92) completed cognitive evaluations and 76% (n=533/706) were followed up to 7.5 years for nursing home placement and mortality. Receiver operator characteristic (ROC) curves were computed to determine sensitivity and specificity for MCI (n=180) and dementia (n=82). Logistic regressions were computed for nursing home placement (n=31) and mortality (n=176). Study 2 participants (N=168; ages 60-90) completed the RCS and SLUMS exam. ROC curves were computed to determine sensitivity and specificity for MCI (n=61) and dementia (n=74). RESULTS: RCS predicted dementia and MCI in study 1 with optimal cutoff scores of ≤ 5 for dementia (sensitivity=0.89, specificity=0.94) and ≤ 7 for MCI (sensitivity=0.87, specificity=0.70). The CDT plus recall predicted dementia and MCI in study 1 with optimal cutoff scores of ≤ 2 for dementia (sensitivity=0.87, specificity=0.85) and ≤ 3 for MCI (sensitivity=0.62, specificity=0.62). Higher RCS scores were protective against nursing home placement and mortality. The RCS predicted dementia and MCI in study 2. CONCLUSIONS: The 3-item RCS exhibits good sensitivity and specificity for the detection of MCI and dementia, and higher cognitive function on the RCS is protective against nursing home placement and mortality. The RCS may be a useful screening instrument for the detection of cognitive dysfunction in the primary care setting.

The Veterans Affairs Saint Louis University mental status exam (SLUMS exam) and the Mini-mental status exam as predictors of mortality and institutionalization.

OBJECTIVE: To evaluate predictive validity of cognitive dysfunction of the Saint Louis University mental status (SLUMS) exam or mini-mental state exam (MMSE) for institutionalization and mortality after 7.5-years. DESIGN: Longitudinal study. SETTING: Geriatric Research, Education and Clinical Center Veterans Affairs Hospital St. Louis, MO. PARTICIPANTS: Patients (N=705) were screened for cognitive dysfunction in 2003 using the SLUMS exam and MMSE, and mortality and institutionalization up to 7.5-years later were evaluated as outcome measures. MEASUREMENT: The associations between outcome measures and MMSE and SLUMS exam total scores, and cognitive status were examined using Kaplan-Meier curves and Cox proportional-hazards regression. RESULTS: Five hundred thirty-three charts were reviewed, 176/533(33%) patients had died and 31/526 (6%) were institutionalized during 7.5-year follow-up period. All subjects were male with a mean age of 75 years and most had high school education or greater (71%). MMSE dementia, SLUMS dementia (ps<.001) and MCI (p<.05) groups had significantly lower survival rates than normal cognition group in the Kaplan-Meier curves. Scores classified as dementia on SLUMS (HR=2.4, 95% CI 1.6-3.7; p <.001) or MMSE (HR=2.3, 95% CI 1.5-3.6; p <.001) both predicted mortality and, also, institutionalization (SLUMS: HR=3.5, 95% CI 1.3-9.1; p <.01; MMSE: HR=3.8, 95% CI 1.6-9.0; p <.001) after adjustment for covariates. Unadjusted SLUMS exam MCI predicted morality (HR=1.5, 95% CI 1.1-2.2; p <.019) but not institutionalization. CONCLUSION: The SLUMS exam and MMSE both predict mortality and institutionalization for male patients screened as positive for dementia.

Beta-amyloid precursor polypeptide in SAMP8 mice affects learning and memory.

Senescence accelerated (SAMP8 [P8]) mice develop age-related deficits in memory and learning. We show that increased expression of amyloid precursor protein (APP) and its mRNA in the hippocampus are also age-related. Immunocytochemical data suggest that a critical amount of APP expression may be needed to generate amyloid (Abeta) protein plaques in the hippocampus. Deficits in acquisition and retention test performance were alleviated by administration of antibody to Abeta protein into the cerebral ventricles. This reversal of cognitive deficits provides a link between increased expression of both APP and Abeta protein and learning and memory loss in these mice.

Visually evoked cortical potentials in awake cats during saccadic eye movements.

Visually evoked potentials (VEPs) measured under conditions of retinal image stabilization that minimized the influences of visual masking and smearing were averaged from electroencephalographic records measured from striate cortex of three cats. The amplitudes of the VEPs increased around saccade initiation. The grating-evoked potentials obtained at different times relative to the saccade exhibited changes in waveform shape that could be attributed to a saccade-evoked potential. The changes in the shape of the waveform were reasonably accounted for by the summation of the grating-evoked potential (produced when the cat did not make a saccade) and an appropriately timed saccade-evoked potential. The fundamental amplitudes of the residual potentials were computed and found to vary across the time course of the saccade. These observations suggest that there are other influences besides visual masking that are exerted early in the visual pathway to modulate visual processing during saccadic eye movements. A corollary discharge process is the most likely candidate to exert these influences.

Alternating monocular exposure increases the spacing of ocularity domains in area 17 of cats.

Goodhill (1993) has recently suggested that the spacing of ocularity domains in visual cortex is not solely an intrinsic property of cortex, but is determined, at least in part, by the degree of correlation in the activity of the two eyes. In support of this model, Löwel (1994) has shown that strabismus, which decorrelates the activity of the two eyes, increases the spacing of ocular dominance columns in area 17, but not area 18, of the cat. As a further test of Goodhill's model, in this paper we examine the effects of another rearing procedure that decorrelates the activity of the two eyes, namely alternating monocular exposure (AME). Cats were reared either normally (9 cats) or with AME (21 cats). We labeled their ocularity domains by one of three methods: ocular dominance columns by 2-deoxyglucose (14 cats), and ocular dominance patches by transneuronal transport (14 cats), or by injections of tracer into single layers of the lateral geniculate nucleus (LGN; 2 cats). The spacing of ocular dominance was 11% greater in the AME cats than in the normal cats (0.976 vs. 0.877 mm). These results are similar to those previously reported for strabismic cats, although the effect is less striking. We thus confirm that decorrelating the activity of the two eyes increases the spacing of cortical ocularity domains. Our results further suggest that the degree of decorrelation affects the extent of that increase.

The monoclonal antibody H386F labels microglia in the retinal nerve fiber layer of several mammals.

The antibody H386F revealed microglia in the retinae of several species: owl monkey, slow loris, galago, ferret, raccoon, and tree shrew. The shape, size, and density of labeled microglia were identical to those labeled by OX-42 and OX-41, two antibodies specific for microglia, in both galago and owl monkey. The labeled microglia varied little in retinal location. There was remarkably little variability in density, shape, number, and size of the labeled microglia between species. All labeled microglia were evenly distributed across, but restricted to, the nerve fiber layer. Possible reasons for this restriction in location are discussed.

Microglia in the nerve fiber layer of the cat retina: detection of postnatal changes by a new monoclonal antibody.

This paper describes changes in the appearance and distribution of microglia in postnatal cat retina as demonstrated by a new antibody, H386F. This fractionated IgM antibody was created via an intrasplenic immunization of a single BALB/C mouse with about 2-3 x 10(5) large, whole cells isolated from 46 minced cat retinae. To confirm that the labeled cells are microglia, the staining properties of H386F were compared with those of four commercially available antibodies, OX-33, OX-41, OX-42, and ED-1, that have been used by others to distinguish between microglia and other cells in rat brain. These experiments show that H386F is the only antibody of the five to label only microglia in both the cat retina and hippocampus.

Effects of aging on the primate visual system: spatial and temporal processing by lateral geniculate neurons in young adult and old rhesus monkeys.

1. Visual abilities decline during normal aging, and many of these declines are due to neural changes in the retina or central visual pathways. We have begun studies of the primate visual system to investigate the location and nature of these changes as well as to answer general questions about the effects of aging on neural function. We began with the dorsal lateral geniculate nucleus (LGN) because it is the main structure through which visual information passes on the way to cortex and because the parallel parvocellular and magnocellular pathways, which may be affected differently by aging, are anatomically distinct there. 2. Single-cell recordings were made in the LGN of young adult (5-16 yr) and old (25-28 yr) rhesus monkeys. We made quantitative measures of a wide variety of response properties for a large number of parvocellular (n = 257) and magnocellular (n = 113) neurons in the two groups of animals. As a result, in addition to studying the effects of aging, we were able to make quantitative comparisons between parvocellular and magnocellular neurons using larger samples than have been studied previously and for some properties that have not been studied before. 3. We found that magnocellular neurons have significantly higher maximal response rates and signal-to-noise ratios than parvocellular neurons. However, response latencies to visual stimulation were similar for neurons in the two types of layers. In agreement with previous studies, magnocellular neurons had higher maximal contrast sensitivity and higher contrast gain than parvocellular neurons. However, the sensitivity difference occurred because nearly all of the neurons with low sensitivities (< 10) were in the parvocellular layers, not because neurons in the magnocellular layers had the highest sensitivities. 4. Neurons with the smallest receptive-field centers, the highest spatial-frequency resolutions, and the highest optimal spatial frequencies were found in the parvocellular layers. However, the overall distributions of each of these properties overlapped substantially for neurons in the two types of layers, and the mean values were not significantly different. The mean high temporal-frequency cutoff was significantly higher for magnocellular than parvocellular neurons, but the difference was small (only 3 Hz), and it occurred because many parvocellular neurons had lower cutoffs than any seen in the magnocellular layers, not because magnocellular neurons had the highest temporal-frequency cutoffs. Parvocellular neurons also had narrower temporal-frequency tuning than magnocellular neurons. However, there was no significant difference in optimal temporal frequency.(ABSTRACT TRUNCATED AT 400 WORDS)

Epidemiological evidence that access to routine optometric care benefits nursing home residents.

Public perception is that nursing home residents receive less than adequate health care. To confirm or refute this view we provided routine optometric services to 47 residents in a nursing home who had ready access to primary medical care. Average refractive error, intraocular pressure, visual acuity, and the prevalence of ocular disease were analyzed. Despite the fact that routine primary medical care was provided in-house and ophthalmologic care was provided on a consultation basis, our study revealed a need for further medical intervention. Seven percent of the patients received a legend prescription for drugs for ocular conditions, whereas 11% received an over-the-counter preparation. Although 11% were already under ophthalmological care, we requested consults from ophthalmology for another 11%. An additional patient was referred to an internist. This study shows that even in nursing homes where residents have access to in-house medical management, routine vision care provided by optometrists can disclose undetected medical problems and improve the quality of life.

Binocular interactions in the cat's dorsal lateral geniculate nucleus, II: Effects on dominant-eye spatial-frequency and contrast processing.

The present study tested the hypothesis that nondominant-eye influences on lateral geniculate nucleus (LGN) neurons affect the processing of spatial and contrast information from the dominant eye. To do this, we determined the effects of stimulating the nondominant eye at its optimal spatial frequency on the responses of LGN cells to sine-wave gratings of different spatial frequency and contrast presented to the dominant eye. Detailed testing was carried out on 49 cells that had statistically significant responses to stimulation of the nondominant eye alone. Spatial-frequency response functions to nondominant-eye stimulation indicated that the responses were spatially tuned, as reported previously (Guido et al., 1989). Optimal spatial frequencies through the nondominant eye were significantly correlated with the optimal spatial frequencies through the dominant eye (r = 0.54; P less than 0.0001), and the optimal spatial frequencies were fairly similar for the two eyes. Nondominant-eye stimulation changed the maximal amplitude of the fundamental (F1) response to dominant-eye stimulation for only about 45% (22 of 49) of the cells that responded to nondominant-eye stimulation alone. The response vs. contrast function through the dominant eye was altered for 73% of the cells (51% independent of spatial frequency). Three types of effects were observed: a change in the initial slope of the response vs. contrast function (contrast gain), a change in the response amplitude at which saturation occurred, or an overall change in response at all contrasts. The incidence of these changes was similar for X and Y cells in LGN layers A, A1, and C (only four W cells were tested). Nondominant-eye stimulation had little or no effect on the sizes or sensitivities of the receptive-field centers or surrounds for the dominant eye. In addition, nondominant-eye stimulation had little or no effect on optimal spatial frequency, spatial resolution, or the bandwidth of spatial-frequency contrast sensitivity curves for the dominant eye. Possible functions of binocular interactions in the LGN are considered. The present results suggest a role in interocular contrast-gain control. Interocular contrast differences can occur before the acquisition of binocular fusion, when the two eyes are viewing different aspects of a visual stimulus. Psychophysical and physiological studies suggest that an interocular mechanism exists to maintain relatively constant binocular interactions despite differences in interocular contrast. The present results suggest that at least part of this mechanism occurs in the LGN.

Binocular interactions in the cat's dorsal lateral geniculate nucleus. I. Spatial-frequency analysis of responses of X, Y, and W cells to nondominant-eye stimulation.

1. X, Y, and W cells in the A and C layers of the cat's dorsal lateral geniculate nucleus (LGN) were tested for responses to stimulation of the nondominant eye. The main purpose was to determine the incidence of nondominant-eye excitation and inhibition among different classes of cells and to examine the spatial-frequency tuning of responses to the nondominant eye. 2. Of 198 cells that were tested with drifting sine-wave gratings presented to the nondominant eye, 109 (55%) showed statistically significant responses. Four types of responses were observed: an increase in the mean discharge rate (F0 excitation), a decrease in the mean discharge rate (F0 inhibition), an increased modulation at the fundamental frequency of the grating (F1 excitation), and a decreased modulation at the fundamental frequency of the grating (F1 inhibition). Overall, 29% of the cells responded with inhibition, 24% responded with excitation, and 2% showed both excitation and inhibition, depending upon the spatial frequency and/or the harmonic response component. The relative incidence of excitation and inhibition was similar for X, Y, and W cells, for cells with on-center and off-center receptive fields, for cells with different receptive-field eccentricities, and for cells in each LGN layer. In addition, within layers A and A1, responses were similar for cells at different distances from the laminar borders. 3. Spatial-frequency response functions indicated that cells could have band-pass or low-pass spatial-frequency tuning through the nondominant eye. Band-pass cells tended to be narrowly tuned (less than or equal to 1 octave), and low-pass cells responded to a broader range of spatial frequencies. These properties were similar for X, Y, and W cells. Spatial resolution tended to be low (less than or equal to 0.8 c/deg for most cells), although a few cells responded to the highest spatial frequency tested (5.4 c/deg). Likewise, optimal spatial frequency was low (less than or equal to 0.2 c/deg) for most cells. These properties were similar for X and Y cells, and there was a weak tendency for X and Y cells to have higher optimal spatial frequencies and spatial resolutions than W cells. 4. In terms of absolute change in activity, responses to drifting gratings were weak. However, cells that were inhibited generally showed 20-60% decreases in activity to the optimal spatial frequency, and cells that were excited generally showed 40-100% increases. Response amplitudes were similar for X, Y, and W cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Binocular competition affects the pattern and intensity of ocular activation columns in the visual cortex of cats.

The effect of binocular competition on the development of ocular activation columns in areas 17 and 18 of cats was studied using the 14C-2-deoxyglucose (14C-2DG) technique to visualize the regions of cortex activated by one eye in cats reared with equal alternating monocular exposure (equal AME), unequal AME, or monocular deprivation (MD). The average size of the ocular activation columns of the eye stimulated during administration of 2DG was positively correlated with the competitive advantage during rearing. In order of increasing percentage of visual cortex activated, the eyes were (1) deprived eye of MD cats, (2) less experienced eye of unequal AME cats, (3) either eye of equal AME cats, (4) more experienced eye of unequal AME cats, and (5) experienced eye of MD cats. In area 17, the shape of the activation columns also was affected by the relative experience of the eye. The columns of the deprived eye of MD cats were widest in layer IV, where they were about the same width as those of the less experienced eye of the unequal AME cats; in other layers they were narrower, sometimes disappearing altogether. In contrast, the activation columns of the less experienced eye of the unequal AME cats were about the same width in all layers. These results suggest that when one eye is placed at a severe disadvantage and receives no patterned input, as in MD, both geniculocortical connections and intracortical connections may be disrupted, but when the disadvantage is less, as in unequal AME, only the geniculocortical connections are disrupted. Binocular competition also affected the intensity of activation within columns in area 17. We used video densitometry to determine ratios of the amount of label in cortical and thalamic structures. Both the ratio of label in area 17 to that in the lateral geniculate nucleus (LGN) and the ratio of label in the binocular segment of area 17 to that in the monocular segment were significantly less for the deprived eye of MD cats than for any other group. These results suggest that even within the smaller activation columns, deprived geniculocortical afferents are relatively ineffective at driving cortical cells. This finding is consistent with earlier reports that the synapses from the deprived pathway are both morphologically abnormal and reduced in number. The cortical labeling for the less experienced eye of the unequal AME cats and the experienced eye of the MD cats were also significantly less than that in equal AME cats.(ABSTRACT TRUNCATED AT 400 WORDS)

W-and Y-cells in the C layers of the cat's lateral geniculate nucleus: normal properties and effects of monocular deprivation.

1. Previous studies have shown that rearing with monocular visual deprivation (MD) produces a loss of Y-cells and a reduction in spatial resolution among X-cells in layers A and A1 of the cat's dorsal lateral geniculate nucleus (dLGN). However, there have been no studies of the effects of visual deprivation on the function of the retinogeniculate W-cell pathway, which terminates in the C layers of the dLGN. It also is not known if Y-cells in the C layers are affected by MD in the same way as Y-cells in the A layers. These questions were addressed by the present experiment. 2. Single-cell recordings were made from the C layers of 5 normal adult cats (112 cells) and from the nondeprived (94 cells) and deprived (95 cells) C layers in 10 cats monocularly deprived by lid suture for 3-7 yr. The cells were classified as X, Y, or W on the basis of their receptive-field properties and responses to electrical stimulation of the optic chiasm. In addition, quantitative measures were made of responses to sine-wave gratings of different spatial frequencies. 3. Receptive-field organization, receptive-field center size, spatial and temporal linearity to counterphased sine-wave gratings, and latency to optic chiasm stimulation were similar for C-layer cells in normal cats and in the deprived and nondeprived layers of MD cats. On the basis of these properties, 23% of normal layer-C cells were classified as Y-cells and 72% were classified as W-cells. The Y-cells tended to be located in the magnocellular division of layer C and most (though not all) W-cells were in the parvocellular division. Normal layers C1 and C2 contained almost exclusively W cells. The incidence of Y and W cells was similar to normal in the nondeprived and deprived C-layers of MD cats. 4. In normal cats, W cells typically had the lowest amplitude first-harmonic (F1) response rates to drifting sine-wave gratings. However, many W cells gave quite brisk responses and, overall, there was no significant difference between F1 response amplitudes of Y and W cells. Response amplitudes of Y- and W-cells in the deprived and nondeprived C-layers of MD cats were not significantly different from normal. 5. Normal Y- and W-cells tended to have low optimal spatial frequencies (0.2 c/deg or lower) and spatial resolutions (generally 0.4-1.6 c/deg) to drifting sine-wave gratings.(ABSTRACT TRUNCATED AT 400 WORDS)

Responses of lateral geniculate neurons that survive long-term visual cortex damage in kittens and adult cats.

Damage to visual cortex (areas 17-19) in kittens or adult cats produces severe retrograde degeneration of neurons in the dorsal lateral geniculate nucleus (LGN). However, some neurons survive in otherwise degenerated portions of the LGN after a visual cortex lesion at any age. Previous studies have shown that there are well-defined differences in potential retinal inputs, soma size, synaptic connections, outputs, and physiological properties of output targets of the surviving LGN cells in cats that received visual cortex damage at different ages. The present experiment investigated the relationships between these differences and the responses of surviving LGN neurons to visual stimulation. Recordings were made from surviving neurons in the degenerated A- and C-layers of the LGN in cats that had received a visual cortex lesion on the day of birth, at 8 weeks of age, or as adults (survival was 11.5-36 months). Normal adult cats were studied for comparison. The visual receptive field was mapped, and tests were carried out to classify each cell as X, Y, or W. In addition, quantitative methods were used to assess response amplitude, strength of receptive-field surround inhibition, spatial-frequency tuning to drifting or counterphased sine-wave gratings, and response to nondominant-eye stimulation for each cell. We found that surviving cells in all LGN layers respond to light, have normal receptive-field organization, and have normal eye dominance following a lesion at any age tested. In addition, gross retinotopic organization of the LGN is normal. However, 2 main abnormalities were observed following a lesion at all 3 ages. First, there is a reduction in the percentage of X cells in the A layers, from 62% in normal LGNs to about 15% in degenerated LGNs. Second, many surviving cells in both the A- and C-layers have abnormally large receptive-field centers. Other differences that were observed between normal A-layer cells and surviving A-layer cells could be attributed to the loss of X cells. These results indicate that cells within a structure that shows severe retrograde degeneration after brain damage can maintain relatively normal function and can take part in potentially important residual neural pathways. Previous studies indicate that these residual pathways can show both anatomical and physiological compensation for the brain damage, and the present findings bear on the consequences and mechanisms of this compensation.

Fluorescent EIA screening of monoclonal antibodies to cell surface antigens.

We have developed a sensitive enzyme immunoassay (EIA) that is useful for detecting antibodies directed against antigenic sites on the surface of mammalian cells. Approximately 100 antigen-bearing cells were trapped in the wells of 96-well Durapore membrane filter plates (Millititer GV plates, Millipore, Bedford, MA). Antibody binding was detected with alkaline phosphatase conjugated goat anti-mouse IgG + IgM. Conjugate alkaline phosphatase activity was detected with a fluorogenic substrate in the presence of levamisole, an inhibitor of endogenous cellular alkaline phosphatase using a Fluoroskan microtiter plate reader (Flow Laboratories). The method permits accurate and reproducible screening of hybridoma supernatants using a minimal number of antigen-bearing cells.

Immunocytochemical staining of cholinergic amacrine cells in rabbit retina.

Cholinergic neurons of rabbit retina were labelled with an antibody against choline acetyltransferase, the synthesizing enzyme for acetylcholine. Two populations of cells are immunoreactive. Type a cell bodies lie in the inner nuclear layer (INL), their dendrites branching narrowly in sublamina a of the inner plexiform layer (IPL), while type b cell bodies lie in the ganglion cell layer (GCL) with dendrites branching in sublamina b of the IPL. The irregular networks of clustered immunoreactive dendrites are similar, but not identical, in the two sublaminae. Type b cells are more numerous than type a cells in central retina. No axons were stained. It appears that the immunoreactive neurons are normally placed and displaced starburst/cholinergic amacrine cells.

Putative cholinergic interneurons in the optic tectum of goldfish.

We have demonstrated that a significant fraction of cells in layer 1 of goldfish optic tectum are immunoreactive for choline acetyltransferase. These cells constitute 4-7% of type XIV cells, which are thought to be intrinsic neurons and represent 95% of all tectal cells. The number of immunoreactive type XIV cells is unchanged following short-term enucleation. The possible integrative role of these putative cholinergic neurons is discussed in relation to sensory functions of the optic tectum.

Choline acetyltransferase immunoreactivity suggests that ganglion cells in the goldfish retina are not cholinergic.

Published evidence that ganglion cells in the retinae of nonmammalian species are cholinergic is strong but indirect. In this paper we report results of attempts to demonstrate choline acetyltransferase immunoreactivity in ganglion cells of goldfish retina using two different antisera against choline acetyltransferase (ChAT), the acetylcholine-synthesizing enzyme. We obtained ChAT-immunoreactive staining of amacrine and displaced amacrine cells in the retina and type XIV cells in the tectum, but we obtained no direct immunocytochemical evidence that ganglion cells in the goldfish retina are cholinergic. Thus, ganglion cells identified by retrograde transport of propidium iodide were never ChAT-immunoreactive. Intraocular injections of colchicine did not result in the appearance of a population of ChAT-immunoreactive neurons in the ganglion cell layer. ChAT-immunoreactive axons were not observed in intact, ligated, or transected optic nerves. And finally, the ChAT immunoreactivity of cells and fibers in the optic tectum was unaffected by deafferentation. These experiments provide no positive evidence that any ganglion cells in goldfish retina contain the acetylcholine-synthesizing enzyme, ChAT. While it is possible that our method is too insensitive to detect the enzyme in ganglion cell somata or too specific to recognize the form of ChAT present in these cells, the fact that we can stain putatively cholinergic retinal amacrine cells and tectal neurons makes these alternative explanations improbable. We conclude that it is unlikely that any of the ganglion cells in the retina are cholinergic and that alternative explanations should be sought for previously published results that suggest that they are.

Immunocytochemical localization of putative cholinergic neurons in the goldfish retina.

The presence of putative cholinergic neurons in goldfish retina was demonstrated by immunocytochemical localization of choline acetyltransferase (ChAT), the synthesizing enzyme for acetylcholine. Four populations of ChAT-immunoreactive neurons were localized: two with cell bodies in the inner nuclear layer and two with cell bodies in the ganglion cell layer. The processes of these neurons ramified in lamina 2 and/or 4 (of 5) in the inner plexiform layer. These cell populations are comparable to populations of putative cholinergic neurons that have been identified by [3H]choline uptake [3, 10].

Effects of unequal alternating monocular exposure on the sizes of cells in the cat's lateral geniculate nucleus.

In unequal alternating monocular exposure, each eye receives normal patterned input, but on alternate days and for unequal periods. This imbalance in stimulation produces a behavioral deficit for the less-experienced eye and alters the ability of that eye to activate cortical cells. To determine whether unequal alternating exposure also affects the sizes of cells in the lateral geniculate nucleus (LGN), we measured the cross-sectional areas of geniculate neurons in seven normally reared cats, 14 cats reared with equal alternating exposure, and 17 cats reared with unequal alternating exposure. We found that, in the LGNs of cats reared with unequal alternating monocular exposure, cells in layers that received their input from the less-experienced eye were smaller than those in layers that received their input from the more-experienced eye. This effect was restricted to the binocular segments of the nucleus, and the difference in cell size was a function of the imbalanced exposure, rather than the length of exposure per se. In control groups given balanced alternating exposure, cell size was not correlated with the length of daily exposure. In cats reared with unequal exposure, the change in cell size was greater in the nucleus ipsilateral to the less-experienced eye. Further, the size of the effect was correlated with the size of the imbalance imposed during rearing: Cats reared with a moderate imbalance (8 hours/day vs. 4 hours/day) showed less change in cell size than cats reared with a large imbalance (8 hours/day vs. 1 hour/day). These results are consistent with those of behavorial and physiological studies and strongly suggest (1) that unequal alternating monocular exposure affects the sizes of cells in the LGN by altering the normal competitive balance between the retinogeniculocortical pathways from the left and right eyes, and (2) that the contralateral pathway has some inherent advantage in this competition. We also found a slight shrinkage of cells in the LGNs of cats reared with equal alternating monocular exposure. Since this effect was restricted to the binocular segments of the nucleus, and was not related to the length of exposure given, it was probably caused by the imbalanced binocular competition that occurred during each day's monocular exposure.