zebrafish-situ-spinal-cord-preparation-for-electrophysiological

Zebrafish <em>In Situ</em> Spinal Cord Preparation for Electrophysiological Recordings from Spinal Sensory and Motor Neurons

Zebrafish, first introduced as a developmental model, have gained popularity in many other fields. The ease of rearing large numbers of rapidly developing ...

University of Colorado Anschutz Medical Campus (UCAMC)

The ability to attend to appropriate stimuli, to plan actions and then alter those actions when environmental conditions change, is essential for an organism to thrive. There is increasing evidence that these executive control processes are mediated in part by N-methyl-D-aspartate receptors (NMDAR). NMDAR subunits confer different physiological properties to the receptor, interact with distinct intracellular postsynaptic scaffolding and signaling molecules and are differentially expressed during development. Recent findings have suggested that the GluN2B subunit may play a unique role in both the acquisition of adaptive choice and the behavioral flexibility required to shift between choices. Here we investigated the role of GluN2B containing NMDARs in the ability to learn, reverse and shift between stimulus dimensions. Mutant mice (floxed-GluN2B x CaMKII-Cre) lacking GluN2B in the dorsal CA1 of the hippocampus and throughout the cortex were tested on an attentional set-shifting task. To explore the role that alterations in motor behavior may have on these behaviors, gross and fine motor behaviors were analyzed in mutant and floxed-control mice. Results show that corticohippocampal loss of GluN2B selectively impaired an initial reversal in a stimulus specific manner and impaired the ability of mutant mice to form an attentional set. Further, GluN2B mice showed normal motor behavior in both overall movement and individual limb behaviors. Together, these results further support the role of NMDAR, and GluN2B in particular, in aspects of executive control including behavioral flexibility and attentional processes.

Conditional loss of GluN2B in cortex and hippocampus impairs attentional set formation.

The hippocampus is heavily involved in the learning and memory processes necessary to successfully encode environmental stimuli and representations over time. Impairment of hippocampal function is associated with numerous neuropsychiatric diseases and can lead to detriments in the quality of life. In order to take full advantage of preclinical models of these disorders, there is a need for the development of more refined measures of clinically relevant hippocampal behaviors. While arena-based navigation tasks have provided fundamental information regarding the role of the hippocampus in spatial memory, the development of automated operant variants have had mixed results. Recently, an automated touch-screen paradigm has been shown to be highly sensitive to hippocampal function in the rat and eliminated mediating strategies that arose in previous tasks. Here we show that mice with lesions encompassing the entire ventral portion of the dorsal hippocampus are impaired on pattern separation behavior using a delayed nonmatching-to-location (TUNL) adapted for mice. Lesioned mice readily acquired the task at control rates when separations were maximal and delay periods were short while decreasing separations significantly impaired lesion mice. However, in contrast to previously reported results in the rat, consistently increasing delays did not significantly impair performance in the lesion group. Presentation of a variable delay within a session significantly impaired performance in lesion mice across delay periods. The current results demonstrate the utility of a touch-screen paradigm for measuring hippocampal-dependent pattern separation in the mouse and establish the paradigm as an important platform for future studies in disease models.

Megan Josey

Neuroscience Graduate Program

University of Colorado Anschutz Medical Campus (UCAMC)

Zebrafish In Situ Spinal Cord Preparation for Electrophysiological Recordings from Spinal Sensory and Motor Neurons

Megan Josey

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University of Colorado Anschutz Medical Campus (UCAMC)

Zebrafish In Situ Spinal Cord Preparation for Electrophysiological Recordings from Spinal Sensory and Motor Neurons

Neuroscience Graduate Program