In addition to providing the basis for color vision, the spectral classes of mammalian cone photoreceptors contribute differentially to other aspects of vision. Specifically, the shortwavelength-sensitive (SWS or "blue-sensitive") cone mechanism differs from other cone mechanisms by exhibiting poorer spatial acuity, low temporal resolution, response saturation at low light levels, longer response latencies, and lack of an off-response (1). The poor spatial acuity has been linked to the low density and unique distribution of SWS cone photoreceptors (2), but the other anomalous characteristics of the SWS cone mechanism usually are attributed to postreceptoral processes (1,3,4). Yet, SWS cones have also been shown to differ biochemically from other cones types. For example, S antigen (also known as 48-kDa protein and arrestin) is present in SWS cones (5), and carbonic anhydrase is absent in SWS cones (6). This study addresses another difference of SWS cones, the pattern of NADPH diaphorase (NADPH dehydrogenase; EC 1.6.99.1) histochemistry in their cellular subcompartments.NADPH diaphorase histochemistry is based on the NADPH-dependent conversion of a soluble tetrazolium salt to an insoluble, visible formazan (7). Neuronal NADPH diaphorase has been shown to be a nitric oxide synthase (NOS) (8, 9) and NADPH diaphorase histochemistry provides a robust method to describe the distribution of NOS in the brain (e.g., ref. 10). As a neural messenger, neuronal nitric oxide (NO) diffuses across cellular membranes to activate soluble guanylate cyclase, which in turn increases intracellular levels of second messenger cGMP (11). NO has been implicated in synaptic transmission and plasticity (12)(13)(14) and also in photoreceptor function (15-18). In the vertebrate retina, NADPHThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact. (27). In no instance has differential staining of spectral classes of cones been reported.In contrast to these previous studies of rod-dominated mammalian retinae, we present work that was undertaken to study NADPH diaphorase histochemistry in a cone-dominated mammalian retina. The tree shrew (Tupaia) has long been of interest to neuroscientists because of its well-developed central visual system and its close taxonomic relationship to primates (28). We elected to study this species because 95% of tree shrew photoreceptors are cones (29) and only two spectral types are represented: SWS and long-wavelength-sensitive (LWS) cones (30,31). Furthermore, the triangular packing distribution and relative density of tree shrew SWS cones are representative of that observed in other mammals, including primates (29,31,32). In addition, the spectral sensitivity and deutan-type dichromatic color vision of this species have been well characterized by electroretinography and psychophysics (33)(34)(35). Thus, the tree shrew retina offers an excellent model to study...

Nitric oxide (NO) is a novel neuronal messenger that likely influences retinal function by activating retinal guanylyl cyclase to increase levels of cGMP. In the present study, the localization of neuronal nitric oxide synthase (nNOS, Type I NOS) in the cone-dominant tree shrew retina was studied using NADPH-d histochemistry and nNOS immunocytochemistry. Both NADPH-d and nNOS-immunoreactivity (IR) labeled the inner segments of rods and the myoids of a regular subpopulation of cones, with their corresponding nuclei outlined. The labeled cone myoids were co-localized with a marker for short-wave-sensitive (SWS) cones (S-antigen) and also displayed the regular triangular packing and density (7%) characteristic of SWS cones in tree shrew and other mammalian retinas. These measures confirmed the identity of the labeled cones as SWS cones. Photoreceptor ellipsoids of all cones were strongly labeled by NADPH-d reactivity, but lacked nNOS-IR. Another novel finding in tree shrew retina was that both NADPH-d and nNOS-IR labeled Muller cells, which have not been labeled by nNOS-IR in other mammalian retinas. Consistent with findings in rod-dominant retinas, two types of amacrine cells at the vitreal edge of the inner nuclear layer and a subpopulation of displaced amacrine cells at the scleral edge of the ganglion cell layer were labeled by both NADPH-d and nNOS-IR. Processes of these labeled cells were seen to extend into the inner plexiform layer, where dense punctate label was seen, especially in the central sublamina. These results show that localization of NOS in the cone-dominant tree shrew retina shares some common properties with rod-dominant mammalian retinas, but also shows some species-specific characteristics. The new finding of nNOS localization in tree shrew SWS cones and rods, but not in other cones, raises interesting questions about the roles of NO in the earliest level of visual processing.

Performance on a variety of cognitive tasks has been reported to decline across the life span. The present research evaluated appetitive instrumental learning in young and mature rats. In Experiment 1, subjects were trained to criterion, placed on extinction training to criterion, and subsequently retrained for a total of three cycles. Results indicated that mature animals were impaired in the initial acquisition of the bar-press response but reacquired the response as quickly as young animals. Resistance to extinction was not significantly impaired in the mature group, both groups increased resistance by the third extinction period, despite the brevity of reinforcement. In Experiment 2, young and mature subjects underwent appetitive instrumental training that continued beyond the acquisition criterion for the first experiment. After the response had been established (to criterion), performance levels were equivalent for young and mature subjects. The number of responses were not significantly different between young and mature groups on the day criterion was met; comparison of number of responses for 4 days after criterion also indicated no significant differences over days of training or between age groups. Examination of the number of responses occurring early in training indicated no significant group difference; hence, the earlier acquisition by young animals in Experiment 1 does not appear to reflect greater activity level in younger animals resulting in earlier and greater exposure to reinforced responses. Results may reflect the contribution of use-induced plasticity, such as long-term potentiation, within brain systems involved in learning and memory. These findings are consistent with evidence of the effects of use and disuse on neurobiological and cognitive function.

These experiments examined the effects of long-term instrumental training on subsequent radial arm maze performance and synaptic transmission within the hippocampal formation. In the first experiment, young (3 mo) and aged (18 mo) male rats underwent 12 weeks of appetitive instrumental conditioning; half were continually reinforced and the other half alternated between reinforcement and extinction. Afterward, spatial cognition was evaluated using an eight-arm radial maze. Subjects undergoing instrumental training performed at rates superior to untrained (control) animals regardless of age or training condition; age-related differences did not exist in the trained groups. In the second experiment, subjects underwent 12 weeks of instrumental training with continuous reinforcement, and excitability of the hippocampus was examined by paired-impulse stimulation of the perforant path. Training enhanced maximal facilitation of population spikes evoked in the granule cell layer of the dentate gyrus of aged subjects to the degree that no statistical difference existed between young and aged animals. Data from untrained control animals indicated a robust decline in paired-impulse excitability in aged subjects. These findings suggest that learning-induced plasticity may attenuate both behavioral and neurobiological changes observed in aged subjects. It is postulated that disuse may underlie some of the cognitive changes exhibited across the life span.

The present research examined the role of hippocampal NMDA-dependent synaptic potentiation on appetitive instrumental conditioning under a continuous reinforcement schedule. In the first experiment, low (.025 mg.kg) or moderate (.05 mg/kg) dosages of the NMDA receptor antagonist, MK801, failed to increase the number of training days required to reach acquisition criterion; number of training days required to reach criterion for extinction were also unaffected. In the second experiment, a higher dosage (.10 mg/kg) of MK801 or induction of long-term potentiation failed to alter the number of responses occurring during acquisition. These data suggest that hippocampal synaptic potentiation does not play a prominent role in instrumental learning with simple contingency conditions. It is suggested that hippocampal LTP reflects a perceptual process that contributes differentially to spatial cognition, classical and instrumental conditioning.