scholarly journals Adult neurogenesis promotes efficient, nonspecific search strategies in a spatial alternation water maze task

2019 ◽  
Author(s):  
Ru Qi Yu ◽  
Matthew Cooke ◽  
Jiaying Zhao ◽  
Jason S. Snyder

AbstractGoal-directed navigation requires learning strategies that are efficient and minimize costs. In some cases it may be desirable to flexibly adjust behavioral responses depending on the cues that vary from one episode to the next. In others, successful navigation might be achieved with inflexible, habit-like responses that reduce cognitive load. Adult neurogenesis is believed to contribute to the spatial processing functions of the hippocampus, particularly when behavioral flexibility is required. However, little is known about the role of neurogenesis in spatial navigation when goals are unpredictable or change according to certain rules. We hypothesized that neurogenesis is necessary in a spatial navigation task that involves different patterns of reinforcement. Intact and neurogenesis-deficient rats were trained to escape to one of two possible platform locations in a spatial water maze. The platform either repeated in the same location for all trials in a day, alternated between two locations across trials, or randomly moved between the two locations. Neurogenesis selectively enhanced escape performance in the alternating condition, but not by improving platform choice accuracy. Instead, neurogenesis-intact rats made fewer search errors and developed an efficient habit-like strategy where they consistently swam to a preferred location. If the platform was not present, they proceeded to the other possible location. In contrast, neurogenesis-deficient rats were indecisive and navigationally less-efficient. Thus, in conditions where goals follow a predictable spatiotemporal pattern, adult neurogenesis promotes the adoption of navigation strategies that are spatially nonspecific but, nonetheless, accurate and efficient.

2021 ◽  
Vol 8 (3) ◽  
pp. 252-268
Author(s):  
Sabrina K Uppal ◽  
◽  
Toni L Uhlendorf ◽  
Ruslan L Nuryyev ◽  
Jacqueline Saenz ◽  
...  

<abstract> <p>It has been established that the CA3 region of the hippocampus is involved in consolidating short-term memory to long-term memory and aids in spatial navigation retention. Seizures and many neurologic diseases induce damage to that region of the hippocampus, resulting in deficits in memory consolidation and spatial navigation. Drug treatments have been proven to have limited effectiveness, but cell replacement therapy has demonstrated to be more promising. Celavie Biosciences have developed a multipotent, nontumorigenic human neural progenitor cell (hNPC) line shown to have the ability to migrate <italic>in situ</italic>, reducing structural and functional deficits in neurodegenerative animal models. Here, we examined whether transplanted hNPCs would reestablish the memories of Han-Wistar rats subjected to hippocampal excitotoxic lesioning. The rats were lesioned in the CA3c regions at 50 days bilaterally with the neurotoxin NMDA (1 µl containing 7.5 mg/ml; −3.5 mm AP; ±2.0 L and −2.5 V). At 54 days of age, live hNPCs (500000 cells in 5 µl cell suspension media), frozen-killed hNPCs (500000 cells/5 µl), HEK293T cells (500000 cells/5 µl) or vehicle (cell suspension media; 5 µl) were bilaterally implanted directly into the NMDA damaged area. The rats were tested two weeks later with three different memory tests: novel and place-object assays and the water-maze task. Results showed that rats receiving live hNPC implantation performed significantly better in the water maze task than control groups; yet, novel and place-object test results showed no significant differences among treatments. Histology confirmed the survival of implanted hNPCs after 28 days post-implantation as well as showing neuroprotective effects. This study showed that Celavie's hNPCs were able to survive and improve some but not all hippocampal functionality, emphasizing the promise for cell replacement therapeutics for neurodegenerative disorders.</p> </abstract>


2020 ◽  
Vol 44 (4) ◽  
pp. 844-855 ◽  
Author(s):  
Neil C. Dodge ◽  
Kevin G. F. Thomas ◽  
Ernesta M. Meintjes ◽  
Christopher D. Molteno ◽  
Joseph L. Jacobson ◽  
...  

2019 ◽  
Author(s):  
Matthew B. Cooke ◽  
Timothy P. O’Leary ◽  
Phelan Harris ◽  
Richard E. Brown ◽  
Jason S. Snyder

AbstractSpatial navigation is a universal behavior that varies depending on goals, experience and available sensory stimuli. Spatial navigational tasks are routinely used to study learning, memory and goal-directed behavior, in both animals and humans. One popular paradigm for testing spatial memory is the Morris water maze, where subjects learn the location of a hidden platform that offers escape from a pool of water. Researchers typically express learning as a function of the latency to escape, though this reveals little about the underlying navigational strategies. Recently, a number of studies have begun to classify water maze search strategies in order to clarify the precise spatial and mnemonic functions of different brain regions, and to identify which aspects of spatial memory are disrupted in disease models. However, despite their usefulness, strategy analyses have not been widely adopted due to the lack of software to automate analyses. To address this need we developed Pathfinder, an open source application for analyzing spatial navigation behaviors. In a representative dataset, we show that Pathfinder effectively characterizes the development of highly-specific spatial search strategies as male and female mice learn a standard spatial water maze. Pathfinder can read data files from commercially- and freely-available software packages, is optimized for classifying search strategies in water maze paradigms, but can also be used to analyze 2D navigation by other species, and in other tasks, as long as timestamped xy coordinates are available. Pathfinder is simple to use, can automatically determine pool and platform geometry, generates heat maps, analyzes navigation with respect to multiple goal locations, and can be updated to accommodate future developments in spatial behavioral analyses. Given these features, Pathfinder may be a useful tool for studying how navigational strategies are regulated by the environment, depend on specific neural circuits, and are altered by pathology.


2005 ◽  
Vol 164 (1) ◽  
pp. 52-60 ◽  
Author(s):  
Thomas Steckler ◽  
Ana F.M. Oliveira ◽  
Chistophe Van Dyck ◽  
Hansfried Van Craenendonck ◽  
Ana M.A. Mateus ◽  
...  

F1000Research ◽  
2020 ◽  
Vol 8 ◽  
pp. 1521
Author(s):  
Matthew B. Cooke ◽  
Timothy P. O'Leary ◽  
Phelan Harris ◽  
Ricky Ma ◽  
Richard E. Brown ◽  
...  

Spatial navigation is a universal behavior that varies depending on goals, experience and available sensory stimuli. Spatial navigational tasks are routinely used to study learning, memory and goal-directed behavior, in both animals and humans. One popular paradigm for testing spatial memory is the Morris water maze, where subjects learn the location of a hidden platform that offers escape from a pool of water. Researchers typically express learning as a function of the latency to escape, though this reveals little about the underlying navigational strategies. Recently, a number of studies have begun to classify water maze search strategies in order to clarify the precise spatial and mnemonic functions of different brain regions, and to identify which aspects of spatial memory are disrupted in disease models. However, despite their usefulness, strategy analyses have not been widely adopted due to the lack of software to automate analyses. To address this need we developed Pathfinder, an open source application for analyzing spatial navigation behaviors. In a representative dataset, we show that Pathfinder effectively characterizes the development of highly-specific spatial search strategies as male and female mice learn a standard spatial water maze. Pathfinder can read data files from commercially- and freely-available software packages, is optimized for classifying search strategies in water maze paradigms, and can also be used to analyze 2D navigation by other species, and in other tasks, as long as timestamped xy coordinates are available. Pathfinder is simple to use, can automatically determine pool and platform geometry, generates heat maps, analyzes navigation with respect to multiple goal locations, and can be updated to accommodate future developments in spatial behavioral analyses. Given these features, Pathfinder may be a useful tool for studying how navigational strategies are regulated by the environment, depend on specific neural circuits, and are altered by pathology.


2019 ◽  
Vol 376 ◽  
pp. 112151 ◽  
Author(s):  
Ru Qi Yu ◽  
Matthew Cooke ◽  
Desiree R. Seib ◽  
Jiaying Zhao ◽  
Jason S. Snyder

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1521 ◽  
Author(s):  
Matthew B. Cooke ◽  
Timothy P. O'Leary ◽  
Phelan Harris ◽  
Richard E. Brown ◽  
Jason S. Snyder

Spatial navigation is a universal behavior that varies depending on goals, experience and available sensory stimuli. Spatial navigational tasks are routinely used to study learning, memory and goal-directed behavior, in both animals and humans. One popular paradigm for testing spatial memory is the Morris water maze, where subjects learn the location of a hidden platform that offers escape from a pool of water. Researchers typically express learning as a function of the latency to escape, though this reveals little about the underlying navigational strategies. Recently, a number of studies have begun to classify water maze search strategies in order to clarify the precise spatial and mnemonic functions of different brain regions, and to identify which aspects of spatial memory are disrupted in disease models. However, despite their usefulness, strategy analyses have not been widely adopted due to the lack of software to automate analyses. To address this need we developed Pathfinder, an open source application for analyzing spatial navigation behaviors. In a representative dataset, we show that Pathfinder effectively characterizes the development of highly-specific spatial search strategies as male and female mice learn a standard spatial water maze. Pathfinder can read data files from commercially- and freely-available software packages, is optimized for classifying search strategies in water maze paradigms, and can also be used to analyze 2D navigation by other species, and in other tasks, as long as timestamped xy coordinates are available. Pathfinder is simple to use, can automatically determine pool and platform geometry, generates heat maps, analyzes navigation with respect to multiple goal locations, and can be updated to accommodate future developments in spatial behavioral analyses. Given these features, Pathfinder may be a useful tool for studying how navigational strategies are regulated by the environment, depend on specific neural circuits, and are altered by pathology.


2003 ◽  
Vol 138 (1) ◽  
pp. 81-94 ◽  
Author(s):  
Timothy E Hoh ◽  
Bryan Kolb ◽  
Ayelet Eppel ◽  
C.H Vanderwolf ◽  
Donald P Cain

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