Loss of Cognitive Flexibility Practice Effects in Female Rats Exposed to Simulated Space Radiation.

During the planned missions to Mars, astronauts will be faced with many potential health hazards including prolonged exposure to space radiation. Ground-based studies have shown that exposure to space radiation impairs the performance of male rats in cognitive flexibility tasks which involve processes that are essential to rapidly and efficiently adapting to different situations. However, there is presently a paucity of information on the effects of space radiation on cognitive flexibility in female rodents. This study has determined the impact that exposure to a low (10 cGy) dose of ions from the simplified 5-ion galactic cosmic ray simulation [https://www.bnl.gov/nsrl/userguide/SimGCRSim.php (07/2023)] (GCRSim) beam or 250 MeV/n 4He ions has on the ability of female Wistar rats to perform in constrained [attentional set shifting (ATSET)] and unconstrained cognitive flexibility (UCFlex) tasks. Female rats exposed to GCRSim exhibited multiple decrements in ATSET performance. Firstly, GCRSim exposure impaired performance in the compound discrimination (CD) stage of the ATSET task. While the ability of rats to identify the rewarded cue was not compromised, the time the rats required to do so significantly increased. Secondly, both 4He and GCRSim exposure reduced the ability of rats to reach criterion in the compound discrimination reversal (CDR) stage. Approximately 20% of the irradiated rats were unable to complete the CDR task; furthermore, the irradiated rats that did reach criterion took more attempts to do so than did the sham-treated animals. Radiation exposure also altered the magnitude and/or nature of practice effects. A comparison of performance metrics from the pre-screen and post-exposure ATSET task revealed that while the sham-treated rats completed the post-exposure CD stage of the ATSET task in 30% less time than for completion of the pre-screen ATSET task, the irradiated rats took 30-50% longer to do so. Similarly, while sham-treated rats completed the CDR stage in ∼10% fewer attempts in the post-exposure task compared to the pre-screen task, in contrast, the 4He- and GCRSim-exposed cohorts took more (∼2-fold) attempts to reach criterion in the post-exposure task than in the pre-screen task. In conclusion, this study demonstrates that female rats are susceptible to radiation-induced loss of performance in the constrained ATSET cognitive flexibility task. Moreover, exposure to radiation leads to multiple performance decrements, including loss of practice effects, an increase in anterograde interference and reduced ability or unwillingness to switch attention. Should similar effects occur in humans, astronauts may have a compromised ability to perform complex tasks.

Impairments and compensation in string-pulling after middle cerebral artery occlusion in the rat.

Stroke is a leading cause of long-term disability in humans, and it is frequently associated with impairments in the skilled use of the arms and hands. Many human upper limb impairments and compensatory changes have been successfully modeled in rodent studies of neocortical stroke, especially those that evaluate single limb use in tasks, such as reaching for food. Humans also use their hands for bilaterally coordinated movements, dependent upon interhemispheric cortical projections, which are also compromised by unilateral stroke. This study describes middle cerebral artery occlusion (MCAO) dependent changes in the bilaterally dependent hand use behavior of string-pulling in the rat. The task involves making hand-over-hand movements to pull down a string that contains a food reward attached to its end. MCAO rats missed the string more often with both hands than Sham rats. When the string was missed on the contralateral to MCAO body side, rats continued to cycle through subcomponents of string-pulling behavior as if the string were grasped in the hand. Rats also failed to make a grasping motion with the contralateral to MCAO hand when the string was missed and instead, demonstrated an open-handed raking-like motions. Nevertheless, with repeated attempts, rats performed components of string-pulling well enough to obtain a reward on the end of the string. Thus, string-pulling behavior is sensitive to bilateral impairments but is achieved with compensatory adjustments following MCAO. These aspects of MCAO string-pulling provide a foundation for studies that investigate the efficacy of therapeutic intervention which might enhance neuroplasticity and recovery.

Multiple decrements in switch task performance in female rats exposed to space radiation.

Astronauts on the Artemis missions to the Moon and Mars will be exposed to unavoidable Galactic Cosmic Radiation (GCR). Studies using male rats suggest that GCR exposure impairs several processes required for cognitive flexibility performance, including attention and task switching. Currently no comparable studies have been conducted with female rats. Given that both males and females will travel into deep space, this study determined whether simulated GCR (GCRsim) exposure impairs task switching performance in female rats. Female Wistar rats exposed to 10 cGy GCRsim (n = 12) and shams (n = 14) were trained to perform a touchscreen-based switch task that mimics a switch task used to evaluate pilots' response times. In comparison to sham rats, three-fold more GCRsim-exposed rats failed to complete the stimulus response stage of training, a high cognitive loading task. In the switch task, 50% of the GCRsim-exposed rats failed to consistently transition between the repeated and switch blocks of stimuli, which they completed during lower cognitive loading training stages. The GCRsim-exposed rats that completed the switch task only performed at 65% of the accuracy of shams. Female rats exposed to GCRsim thus exhibit multiple decrements in the switch task under high, but not low, cognitive loading conditions. While the operational significance of this performance decrement is unknown, if GCRSim exposure was to induce similar effects in astronauts, our data suggests there may be a reduced ability to execute task switching under high cognitive loading situations.

Spatial Disorientation Under Dark Conditions Across Development in an Alzheimer's Disease Mouse Model.

Alzheimer's disease (AD) is associated with hippocampal neuropathology and cognitive impairments, including wandering behavior or becoming lost in a familiar environment. Wandering behavior is severe and manifests early in life for people with specific genetic mutations. Genetic mouse models of AD have been developed to characterize the onset and progression of behavioral deficits that represent human behaviors, such as wandering, to test the efficacy of therapeutics. It is not clear if current assessments of mouse models capture the onset of AD or a snapshot of its progression. Sequential analysis of open field behavior provides a robust, quick test to dissociate navigation cues that contribute to spatial disorientation, a feature of wandering. Despite potential utility in evaluating this feature of AD, little work has been reported using animal models of dementia in this task. Thus, we examined the use of different sources of information to maintain spatial orientation at two prodromal ages in female transgenic CRND8 AD (n = 17) and Control mice (n = 16). These mice exhibit amyloid plaques, a hallmark neuropathological feature of AD, that are associated with cognitive dysfunction at ∼three months of age. Spatial disorientation was observed at two months and more severely at four months under dark conditions, but performance was spared when visual environmental cues were available. This study provides documentation of impaired self-movement cue processing in AD mice, establishing the dark open field as a behavioral tool to characterize spatial disorientation associated with AD. These findings may accelerate future assessments of novel therapeutic interventions for neurological disorders.

Fine motor deficits exhibited in rat string-pulling behavior following exposure to sleep fragmentation and deep space radiation.

Deep space flight missions will expose astronauts to multiple stressors, including sleep fragmentation and space radiation. There is debate over whether sleep disruptions are an issue in deep space. While these stressors independently impair sensorimotor function, the combined effects on performance are currently unknown. String-pulling behavior involves highly organized bimanual reach-to-grasp and withdraw movements. This behavior was examined under rested wakeful conditions and immediately following one session of sleep fragmentation in Sham and irradiated rats 3 months after exposure (10 cGy 4Helium or 5-ion simulated Galactic Cosmic Radiation). Sleep fragmentation disrupted several aspects of string-pulling behavior, such that rats' ability to grasp the string was reduced, reach endpoint concentration was more variable, and distance traveled by the nose increased in the Y-range compared to rested wakeful performance. Overall, irradiated rats missed the string more than Sham rats 3 months post-exposure. Irradiated rats also exhibited differential impairments at 3 months, with additional deficits unveiled after sleep fragmentation. 4Helium-exposed rats took longer to approach the string after sleep fragmentation. Further, rats exposed to 4Helium traveled shorter withdraw distances 3 months after irradiation, while this only emerged in the other irradiated group after sleep fragmentation. These findings identify sleep fragmentation as a risk for fine motor dysfunction in Sham and irradiated conditions, in addition to radiation exposure. There may be complex temporal alterations in performance that are stressor- and ion-dependent. Thus, it is critical to implement appropriate models of multi-flight stressors and performance assessments in preparation for future deep space flight missions.

Sex-specific effects of ethanol consumption in older Fischer 344 rats on microglial dynamics and Aß(1-42) accumulation.

Chronic alcohol consumption, Alzheimer's disease (AD), and vascular dementia are all associated with cognitive decline later in life, raising questions about whether their underlying neuropathology may share some common features. Indeed, recent evidence suggests that ethanol exposure during adolescence or intermittent drinking in young adulthood increased neuropathological markers of AD, including both tau phosphorylation and beta-amyloid (Aß) accumulation. The goal of the present study was to determine whether alcohol consumption later in life, a time when microglia and other neuroimmune processes tend to become overactive, would influence microglial clearance of Aß(1-42), focusing specifically on microglia in close proximity to the neurovasculature. To do this, male and female Fischer 344 rats were exposed to a combination of voluntary and involuntary ethanol consumption from ∼10 months of age through ∼14 months of age. Immunofluorescence revealed profound sex differences in microglial co-localization, with Aß(1-42) showing that aged female rats with a history of ethanol consumption had a higher number of iba1+ cells and marginally reduced expression of Aß(1-42), suggesting greater phagocytic activity of Aß(1-42) among females after chronic ethanol consumption later in life. Interestingly, these effects were most prominent in Iba1+ cells near neurovasculature that was stained with tomato lectin. In contrast, no significant effects of ethanol consumption were observed on any markers in males. These findings are among the first reports of a sex-specific increase in microglia-mediated phagocytosis of Aß(1-42) by perivascular microglia in aged, ethanol-consuming rats, and may have important implications for understanding mechanisms of cognitive decline associated with chronic drinking.

Similar Loss of Executive Function Performance after Exposure to Low (10 cGy) Doses of Single (4He) Ions and the Multi-Ion GCRSim Beam.

While astronauts are trained to deal with multiple issues that they are likely to encounter during a mission, it is likely that some problems will arise that astronauts have no direct experience in resolving. During International Space Station (ISS) missions, astronauts can rely on Mission Control to help resolve complex problems, however during the long-duration space missions planned to the Moon and Mars, astronauts will have to act more autonomously, thus the ability of astronauts to conduct executive function will be critical for problem solving during deep space missions. Several studies have shown that exposure to space radiation results in decreased executive function performance. However, to date these studies have used single ions, whereas there is a complex mixture of ion species and energies within the space-radiation spectrum that astronauts will be exposed to. Thus, there is some concern that the neurocognitive impairments reported from single ion studies will not be representative of the severity, frequency or nature of cognitive deficits that arise following exposure to more complex space-radiation spectra. The current study has determined the relative impact that isodoses of He ions or the simplified 6-ion-galactic cosmic ray simulation (GCRSim) beams had on the performance of male Wistar rats in executive function tasks, attentional set shifting (ATSET) task and unconstrained cognitive flexibility (UCFlex). Exposure to 10 cGy GCRSim induced performance deficits in the simple discrimination (SD) stage of the ATSET task, which appears to be universally impacted by all space-radiation ions studied to date. The magnitude of the SD performance decrements in the GCRSim-irradiated rats were comparable to those observed in He-irradiated rats. Importantly, space-radiation exposure does not appear to decrease the ability of rats to identify the key cues in the ATSET task, but increased the time/number of iterations required to successfully find the solution. Practice effect (PE) analysis (comparing prescreen to the postirradiation SD performance) revealed that while the sham-treated rats completed the second ATSET task in 30% less time than they did the prescreen ATSET test (despite the perceptual domain of the relevant (rewarded) cue being changed), the space-radiation-exposed rats took 50% longer to do so. The space-radiation-induced delay in problem solving was not confined to the ATSET task, but was also observed when rats were screened for UCFlex performance. Should similar changes occur in astronauts, these data raise the possibility that space-radiation exposure would reduce in-flight improvement in performance in repetitive tasks (PE) and may lead to a reduced ability to utilize transitive inference from "similar" problems to solve issues that have not been previously encountered.

Similar Loss of Executive Function Performance after Exposure to Low (10 cGy) Doses of Single (4He) Ions and the Multi-Ion GCRSim Beam.

While astronauts are trained to deal with multiple issues that they are likely to encounter during a mission, it is likely that some problems will arise that astronauts have no direct experience in resolving. During International Space Station (ISS) missions, astronauts can rely on Mission Control to help resolve complex problems, however during the long-duration space missions planned to the Moon and Mars, astronauts will have to act more autonomously, thus the ability of astronauts to conduct executive function will be critical for problem solving during deep space missions. Several studies have shown that exposure to space radiation results in decreased executive function performance. However, to date these studies have used single ions, whereas there is a complex mixture of ion species and energies within the space-radiation spectrum that astronauts will be exposed to. Thus, there is some concern that the neurocognitive impairments reported from single ion studies will not be representative of the severity, frequency or nature of cognitive deficits that arise following exposure to more complex space-radiation spectra. The current study has determined the relative impact that isodoses of He ions or the simplified 6-ion-galactic cosmic ray simulation (GCRSim) beams had on the performance of male Wistar rats in executive function tasks, attentional set shifting (ATSET) task and unconstrained cognitive flexibility (UCFlex). Exposure to 10 cGy GCRSim induced performance deficits in the simple discrimination (SD) stage of the ATSET task, which appears to be universally impacted by all space-radiation ions studied to date. The magnitude of the SD performance decrements in the GCRSim-irradiated rats were comparable to those observed in He-irradiated rats. Importantly, space-radiation exposure does not appear to decrease the ability of rats to identify the key cues in the ATSET task, but increased the time/number of iterations required to successfully find the solution. Practice effect (PE) analysis (comparing prescreen to the postirradiation SD performance) revealed that while the sham-treated rats completed the second ATSET task in 30% less time than they did the prescreen ATSET test (despite the perceptual domain of the relevant (rewarded) cue being changed), the space-radiation-exposed rats took 50% longer to do so. The space-radiation-induced delay in problem solving was not confined to the ATSET task, but was also observed when rats were screened for UCFlex performance. Should similar changes occur in astronauts, these data raise the possibility that space-radiation exposure would reduce in-flight improvement in performance in repetitive tasks (PE) and may lead to a reduced ability to utilize transitive inference from "similar" problems to solve issues that have not been previously encountered.

Rapid loss of fine motor skills after low dose space radiation exposure.

Sensorimotor function, motivation, and attentional processes are fundamental aspects of behavioral organization during skilled tasks. NASA's planned expedition to Mars will expose astronauts to space radiation (SR) that has the potential to impair performance in mission critical tasks. Impairments in task accuracy and movement kinematics have been previously reported during string-pulling behavior ~7 months after SR exposure. If similar SR-induced sensorimotor deficits emerge at earlier times, then astronauts may have compromised in-flight performance disruptions while performing skilled tasks in critical situations, such as when manipulating controls or performing seat egress. Due to the possibility that such performance losses may compromise mission success, it is critical to determine if sensorimotor, motivation, or attentional deficits occur acutely after SR exposure at a time point that corresponds to in-flight performance. Male Wistar rats were thus exposed to either 10 cGy simplified galactic cosmic radiation (GCRsim), 10 cGy 4Helium (4He), or no radiation at all (Sham), and string-pulling behavior was assessed approximately 72 h later. Following exposure to SR, rats (4He) took more time to approach the string to initiate string-pulling behavior and to pull in the string to reach the Cheerio (4He and GCRsim) relative to Sham rats. 4He-exposed rats also exhibited a greater number of misses and less contacts relative to both Sham and GCRsim-exposed rats. Further, rats exposed to 4He demonstrated less concentrated reach endpoints with both the left and right hands compared to GCR-exposed rats. This work suggests that sensorimotor function and motivation and/or attentional processes were impaired 72 h after 4He-radiation exposure.

Exposure to 5 cGy 28Si Particles Induces Long-Term Microglial Activation in the Striatum and Subventricular Zone and Concomitant Neurogenic Suppression.

The proposed mission to Mars will expose astronauts to space radiation that is known to adversely affect cognition and tasks that rely on fine sensorimotor function. Space radiation has also been shown to affect the microglial and neurogenic responses in the central nervous system (CNS). We recently reported that a low dose of 5 cGy 600 MeV/n 28Si results in impaired cognition and skilled motor behavior in adult rats. Since these tasks rely at least in part on the proper functioning of the striatum, we examined striatal microglial cells in these same subjects. Using morphometric analysis, we found that 28Si exposure increased activated microglial cells in the striatum. The majority of these striatal Iba1+ microglia were ED1-, indicating that they were in an alternatively activated state, where microglia do not have phagocytic activity but may be releasing cytokines that could negatively impact neuronal function. In the other areas studied, Iba1+ microglial cells were increased in the subventricular zone (SVZ), but not in the dentate gyrus (DG). Additionally, we examined the relationship between the microglial response and neurogenesis. An analysis of new neurons in the DG revealed an increase in doublecortin-positive (DCX+) hilar ectopic granule cells (hEGC) which correlated with Iba1+ cells, suggesting that microglial cells contributed to this aberrant distribution which may adversely affect hippocampal function. Taken together, these results indicate that a single dose of 28Si radiation results in persistent cellular effects in the CNS that may impact astronauts both in the short and long-term following deep space missions.

Organization of exploratory behavior under dark conditions in female and male rats.

Sexually dimorphic performance has been observed across humans and rodents in many spatial tasks. In general, these spatial tasks do not dissociate the use of environmental and self-movement cues. Previous work has demonstrated a role for self-movement cue processing in organizing open field behavior; however, these studies have not directly compared female and male movement characteristics. The current study examined the organization of open field behavior under dark conditions in female and male rats. Significant differences between female and male rats were observed in the location of stopping behavior relative to a cue and the topography exhibited during lateral movements. In contrast, no sex differences were observed on measures used to detect self-movement cue processing deficits. These results provide evidence that female and male rats are similar in their use of self-movement cues to organize open field behavior; however, other factors may be contributing to differences in performance.

Effects of acquired vestibular pathology on the organization of mouse exploratory behavior.

Rodent open field behavior is highly organized and occurs spontaneously in novel environments. This organization is disrupted in mice with vestibular pathology, suggesting vestibular signals provide important contributions to this behavior. A caveat to this interpretation is that previous studies have investigated open field behavior in adult mice with congenital vestibular dysfunction, and the observed deficits may have resulted from developmental changes instead of the lack of vestibular signals. To determine which aspects of open field behavior depend specifically on vestibular signals, mouse movement organization was examined under dark and light conditions at two time points, 1 and 2 months, after bilateral chemical labyrinthectomy. Our results show that acquired vestibular damage selectively disrupted the organization of open field behavior. Access to visual environmental cues attenuated, but did not eliminate, these significant group differences. Improvement in movement organization from the first to the second testing session was limited to progression path circuity. These observations provide evidence for the role of the vestibular system in maintaining spatial orientation and establishes a foundation to investigate neuroplasticity in brain systems that process self-movement information.

Skilled movement and posture deficits in rat string-pulling behavior following low dose space radiation (28Si) exposure.

Deep space flight missions beyond the Van Allen belt have the potential to expose astronauts to space radiation which may damage the central nervous system and impair function. The proposed mission to Mars will be the longest mission-to-date and identifying mission critical tasks that are sensitive to space radiation is important for developing and evaluating the efficacy of counter measures. Fine motor control has been assessed in humans, rats, and many other species using string-pulling behavior. For example, focal cortical damage has been previously shown to disrupt the topographic (i.e., path circuity) and kinematic (i.e., moment-to-moment speed) organization of rat string-pulling behavior count to compromise task accuracy. In the current study, rats were exposed to a ground-based model of simulated space radiation (5 cGy 28Silicon), and string-pulling behavior was used to assess fine motor control. Irradiated rats initially took longer to pull an unweighted string into a cage, exhibited impaired accuracy in grasping the string, and displayed postural deficits. Once rats were switched to a weighted string, some deficits lessened but postural instability remained. These results demonstrate that a single exposure to a low dose of space radiation disrupts skilled hand movements and posture, suggestive of neural impairment. This work establishes a foundation for future studies to investigate the neural structures and circuits involved in fine motor control and to examine the effectiveness of counter measures to attenuate the effects of space radiation on fine motor control.

Effects of string length on the organization of rat string-pulling behavior.

The string-pulling paradigm has been adapted to investigate many psychological phenomena across a range of animal species. Although varying string length has been shown to influence performance, the nature of the representation remains to be determined. Across three experiments, rats were shaped to pull string to receive food reinforcement. Either string length or reinforcement rate was manipulated to examine the influence on string-pulling behavior. Experiment 1 demonstrated that varied string length was sufficient to elicit an odor discrimination. Subsequent experiments provided evidence that varying string length (Experiment 2) and reinforcement rate (Experiment 3) produced qualitatively distinct patterns of string-pulling behavior. In Experiment 2 rats that received a long string were more likely to pull in the probe string to the end, yet no differences were observed in approach time between short and long groups. However, in Experiment 3 rats that received low reinforcement were less likely to pull in the probe string to the end and were slower to approach the string to begin pulling. These results are consistent with rats using temporal and motivational characteristics to guide responding during string-pulling behavior.

Human string-pulling with and without a string: movement, sensory control, and memory.

String-pulling is a behavior that is allied to many daily acts and is an easily performed action featuring hand-over-hand movements to reel in a string (or rope). String-pulling has been used as a test of perceptual and cognitive functions in many animal species, including human children, but its movements and sensory control have not been characterized. Male and female university students (n = 68) performed target-based or memory-based string-pulling in which they pulled down a string suspended on an overhead pulley and immediately afterwards attempted to make the same movement in a memory-based test. Frame-by-frame video scoring was used to describe movements, eye-tracking and visual occluding glasses were used to assess sensory control, and a Matlab video-analysis procedure was used to describe kinematics. The string was advanced using five arm/hand movements: with lift and advance comprising fast up movements, and grasp, pull and push comprising slow down movements. Fingers closed 5 (pinky) through 1 (thumb) to make a whole-hand grasp and release in target-based string pulling but moved in a reverse sequence for the memory-based task. Target-based string pulling was not visually guided unless participants were instructed to grasp at a cue, and then vision featured eye-tracking of the target and pupil dilation with the grasp, but there was no relation between eye events for memory-based string-pulling. For target-based string-pulling the left and right hands advanced the string with both independent and concurrent movement but only independent movements were featured in a more symmetrical memory-based movement. The results are discussed in relation to the sensory control of hand movements, contemporary theories of the neural control of hand movements, and species differences in string-pulling.

The structure of arm and hand movements in a spontaneous and food rewarded on-line string-pulling task by the mouse.

Arm and hand use by the mouse have been studied in a variety of tasks in order to understand the structure of skilled movements and motor learning, the anatomy and function of neural pathways, and to develop animal models of neurological conditions. The present study describes string-pulling by the mouse, a behavior in which a mouse uses hand-over-hand movements to pull down a string that hangs from the top of a test cage. Mice both spontaneously string-pull and also string-pull to obtain cashew nuts tied to the end of the string as food reward. To string-pull, mice sat upright and tracked the string with their nose and then made hand-over-hand movements to reel in the string. A string-pull movement consists of four arm movements (Advance to make purchase, Pull, Push to draw the string down and Lift to return the hand for the next Advance) and four hand movements (Collect to aim the hand, Overgrasp to position the hand, and Grasp to make purchase, and Release). The kinematic profiles of the string-pull movement are distinctive with each hand making similar movements at a rate of 4 cycles per second and with the Lift and Advance movements occurring at a higher speed than Pull and Push movements. The results are discussed in relation to the antecedent repertoire of mouse behavior that lends itself to string-pulling, with respect to the utility of using string-pulling to investigate motor systems and adapting string-pulling to model neurological conditions in mice.

Unilateral forelimb sensorimotor cortex devascularization disrupts the topographic and kinematic characteristics of hand movements while string-pulling for food in the rat.

String-pulling by the rat is a bimanual act, in which an upright animal retrieves a piece of food attached to the end of the string by downward hand-over-hand movements. The present study compared the movements of string-pulling, using topographic and kinematic measures of hand movement, in control rats and rats with unilateral sensorimotor motor cortex lesion produced by removal of the pia matter. In the first week following devascularization, the rhythmicity and accuracy of string-pulling movements decomposed; however, thereafter the rhythm of bilateral alternation was restored. Over 70days of testing, distance traveled decreased for both hands in the control and lesion groups, suggesting that both groups displayed an increase in string-pulling efficiency. Nevertheless, the lesion group exhibited more missed string contacts with the (contralateral-to-lesion) hand and more grasps in which the string was hooked between the digits with both hands. In addition, an increase in mouth grasps was observed in the lesion group. Motion capture analyses revealed that the lesion group exhibited longer reach and withdraw movements and these movements were longer for the ipsilateral-to-lesion vs contralateral-to-lesion hand. Thus, although rhythmicity of string-pulling behavior recovers after sensorimotor cortex devascularization, the contralateral-to-lesion hand contributed less to string pulling and requires mouth grasps to stabilize the string for grasping. The results are discussed in relation to contemporary theories of the contributions of the forelimb motor cortex to skilled movement and the potential use of string-pulling as a therapy for brain injury.

A history of adolescent binge drinking in humans is associated with impaired self-movement cue processing on manipulatory scale navigation tasks.

A binge drinking pattern of alcohol consumption has been shown to have an impact on brain structures that continue to develop into late adolescence. These same brain structures have been implicated in processing self-movement cues. The current study applies an array of existing and novel kinematic analysis techniques to characterize performance on manipulatory scale tasks to assess spatial orientation deficits associated with a history of adolescent binge drinking. Using kinematic analysis techniques, a history of adolescent binge drinking in university students was associated with disruptions in outward segment movement organization and less accurate direction and distance estimation in a dead reckoning task. Similar disruptions in performance were found in the bead maze task in the first training block; however, no group differences were observed on subsequent blocks of place training. This is the first study to demonstrate a relationship between adolescent binge drinking in humans and impaired processing of self-movement cues. This pattern of results demonstrates the potential of manipulatory-scale spatial tasks to detect differences in information processing associated with factors known to disrupt normal central nervous system development.

Cholinergic deafferentation of the hippocampus causes non-temporally graded retrograde amnesia in an odor discrimination task.

Dementia of the Alzheimer's type (DAT) is a neurodegenerative disorder marked by loss of hippocampal cholinergic tone and significant memory impairments, specifically for memories acquired prior to disease onset. The nature of this relationship, however, remains debated. The current study used the string pulling task to evaluate the temporal effects of odor discrimination learning in animals with selective cholinergic lesions to determine the role of the septohippocampal cholinergic system in mnemonic function. Rats with 192-IgG-Saporin lesions to the medial septum had a higher number of correct responses in the reversal training when compared to sham rats, suggesting an inability to retrieve the previously learned discrimination; however, no temporal gradient was observed. Furthermore, there were no group differences when learning a novel odor discrimination, demonstrating the ability for all rats to form new memories. These results establish a role for the cholinergic medial septum projections in long-term memory retrieval. The current study provides a behavioral assessment technique to investigate factors that influence mnemonic deficits associated with rodent models of DAT.

Otolithic information is required for homing in the mouse.

Navigation and the underlying brain signals are influenced by various allothetic and idiothetic cues, depending on environmental conditions and task demands. Visual landmarks typically control navigation in familiar environments but, in the absence of landmarks, self-movement cues are able to guide navigation relatively accurately. These self-movement cues include signals from the vestibular system, and may originate in the semicircular canals or otolith organs. Here, we tested the otolithic contribution to navigation on a food-hoarding task in darkness and in light. The dark test prevented the use of visual cues and thus favored the use of self-movement information, whereas the light test allowed the use of both visual and non-visual cues. In darkness, tilted mice made shorter-duration stops during the outward journey, and made more circuitous homeward journeys than control mice; heading error, trip duration, and peak error were greater for tilted mice than for controls. In light, tilted mice also showed more circuitous homeward trips, but appeared to correct for errors during the journey; heading error, trip duration, and peak error were similar between groups. These results suggest that signals from the otolith organs are necessary for accurate homing performance in mice, with the greatest contribution in non-visual environments.