Passive exposure to visual motion leads to short-term changes in the optomotor response of aging zebrafish.

Numerous studies have shown that prior visual experiences play an important role in sensory processing and adapting behavior in a dynamic environment. A repeated and passive presentation of visual stimulus is one of the simplest procedures to manipulate acquired experiences. Using this approach, we aimed to investigate exposure-based visual learning of aging zebrafish and how cholinergic intervention is involved in exposure-induced changes. Our measurements included younger and older wild-type zebrafish and achesb55/+ mutants with decreased acetylcholinesterase activity. We examined both within-session and across-day changes in the zebrafish optomotor responses to repeated and passive exposure to visual motion. Our findings revealed short-term (within-session) changes in the magnitude of optomotor response (i.e., the amount of position shift by fish as a response to visual motion) rather than long-term and persistent effects across days. Moreover, the observed short-term changes were age- and genotype-dependent. Compared to the initial presentations of motion within a session, the magnitude of optomotor response to terminal presentations decreased in the older zebrafish. There was a similar robust decrease specific to achesb55/+ mutants. Taken together, these results point to short-term (within-session) alterations in the motion detection of adult zebrafish and suggest differential effects of neural aging and cholinergic system on the observed changes. These findings further provide important insights into adult zebrafish optomotor response to visual motion and contribute to understanding this reflexive behavior in the short- and long-term stimulation profiles.

Long-Term Acetylcholinesterase Depletion Alters the Levels of Key Synaptic Proteins while Maintaining Neuronal Markers in the Aging Zebrafish (Danio rerio) Brain.

INTRODUCTION: Interventions targeting cholinergic neurotransmission like acetylcholinesterase (AChE) inhibition distinguish potential mechanisms to delay age-related impairments and attenuate deficits related to neurodegenerative diseases. However, the chronic effects of these interventions are not well described. METHODS: In the current study, global levels of cholinergic, cellular, synaptic, and inflammation-mediating proteins were assessed within the context of aging and chronic reduction of AChE activity. Long-term depletion of AChE activity was induced by using a mutant zebrafish line, and they were compared with the wildtype group at young and old ages. RESULTS: Results demonstrated that AChE activity was lower in both young and old mutants, and this decrease coincided with a reduction in ACh content. Additionally, an overall age-related reduction in AChE activity and the AChE/ACh ratio was observed, and this decline was more prominent in wildtype groups. The levels of an immature neuronal marker were upregulated in mutants, while a glial marker showed an overall reduction. Mutants had preserved levels of inhibitory and presynaptic elements with aging, whereas glutamate receptor subunit levels declined. CONCLUSION: Long-term AChE activity depletion induces synaptic and cellular alterations. These data provide further insights into molecular targets and adaptive responses following the long-term reduction of AChE activity that was also targeted pharmacologically to treat neurodegenerative diseases in human subjects.

Zebrafish optomotor response to second-order motion illustrates that age-related changes in motion detection depend on the activated motion system.

Various aspects of visual functioning, including motion perception, change with age. Yet, there is a lack of comprehensive understanding of age-related alterations at different stages of motion processing and in each motion system. To understand the effects of aging on second-order motion processing, we investigated optomotor responses (OMR) in younger and older wild-type (AB-strain) and acetylcholinesterase (achesb55/+) mutant zebrafish. The mutant fish with decreased levels of acetylcholinesterase have been shown to have delayed age-related cognitive decline. Compared to previous results on first-order motion, we found distinct changes in OMR to second-order motion. The polarity of OMR was dependent on age, such that second-order stimulation led to mainly negative OMR in the younger group while older zebrafish had positive responses. Hence, these findings revealed an overall aging effect on the detection of second-order motion. Moreover, neither the genotype of zebrafish nor the spatial frequency of motion significantly changed the response magnitude. Our findings support the view that age-related changes in motion detection depend on the activated motion system.

The optomotor response of aging zebrafish reveals a complex relationship between visual motion characteristics and cholinergic system.

Understanding the principles underlying age-related changes in motion perception is paramount for improving the quality of life and health of older adults. However, the mechanisms underlying age-related alterations in this aspect of vision, which is essential for survival in a dynamic world, still remain unclear. Using optomotor responses to drifting gratings, we investigated age-related changes in motion detection of adult zebrafish (wild-type/AB-strain and achesb55/+ mutants with decreased levels of acetylcholinesterase). Our results pointed out negative optomotor responses that significantly depend on the spatial frequency and contrast level of stimulation, providing supporting evidence for the visual motion-driven aspect of this behavior mainly exhibited by adult zebrafish. Although there were no significant main effects of age and genotype, we found a significant three-way interaction between contrast level, age, and genotype. In the contrast domain, the changes in optomotor responses and thus in the detection of motion direction were age- and genotype-specific. Accordingly, these behavioral findings suggest a strong but complicated relationship between visual motion characteristics and the cholinergic system during neural aging.

The relationship between co-speech gesture production and macrolinguistic discourse abilities in people with focal brain injury.

Brain damage is associated with linguistic deficits and might alter co-speech gesture production. Gesture production after focal brain injury has been mainly investigated with respect to intrasentential rather than discourse-level linguistic processing. In this study, we examined 1) spontaneous gesture production patterns of people with left hemisphere damage (LHD) or right hemisphere damage (RHD) in a narrative setting, 2) the neural structures associated with deviations in spontaneous gesture production in these groups, and 3) the relationship between spontaneous gesture production and discourse level linguistic processes (narrative complexity and evaluation competence). Individuals with LHD or RHD (17 people in each group) and neurotypical controls (n = 13) narrated a story from a picture book. Results showed that increase in gesture production for LHD individuals was associated with less complex narratives and lesions of individuals who produced more gestures than neurotypical individuals overlapped in frontal-temporal structures and basal ganglia. Co-speech gesture production of RHD individuals positively correlated with their evaluation competence in narrative. Lesions of RHD individuals who produced more gestures overlapped in the superior temporal gyrus and the inferior parietal lobule. Overall, LHD individuals produced more gestures than neurotypical individuals. The groups did not differ in their use of different gesture forms except that LHD individuals produced more deictic gestures per utterance than RHD individuals and controls. Our findings are consistent with the hypothesis that co-speech gesture production interacts with macro-linguistic levels of discourse and this interaction is affected by the hemispheric lateralization of discourse abilities.

Narratives of focal brain injured individuals: A macro-level analysis.

Focal brain injury can have detrimental effects on the pragmatics of communication. This study examined narrative production by unilateral brain damaged people (n=36) and healthy controls and focused on the complexity (content and coherence) and the evaluative aspect of their narratives to test the general hypothesis that the left hemisphere is biased to process microlinguistic information and the right hemisphere is biased to process macrolinguistic information. We found that people with left hemisphere damage's (LHD) narratives were less likely to maintain the overall theme of the story and produced fewer evaluative comments in their narratives. These deficits correlated with their performances on microlinguistic linguistic tasks. People with the right hemisphere damage (RHD) seemed to be preserved in expressing narrative complexity and evaluations as a group. Yet, single case analyses revealed that particular regions in the right hemisphere such as damage to the dorsolateral prefrontal cortex (DLPFC), the anterior and superior temporal gyrus, the middle temporal gyrus, and the supramarginal gyrus lead to problems in creating narratives. Our findings demonstrate that both hemispheres are necessary to produce competent narrative production. LHD people's poor production is related to their microlinguistic language problems whereas RHD people's impaired abilities can be associated with planning and working memory abilities required to relate events in a narrative.