Complex Genetics of Behavior: BXDs in the Automated Home-Cage

Abstract

This chapter describes a use case for the genetic dissection and automated analysis of complex behavioral traits using the genetically diverse panel of BXD mouse recombinant inbred strains. Strains of the BXD resource differ widely in terms of gene and protein expression in the brain, as well as in their behavioral repertoire. A large mouse resource opens the possibility for gene finding studies underlying distinct behavioral phenotypes, however, such a resource poses a challenge in behavioral phenotyping. To address the specifics of large-scale screening we describe how to investigate: (1) how to assess mouse behavior systematically in addressing a large genetic cohort, (2) how to dissect automation-derived longitudinal mouse behavior into quantitative parameters, and (3) how to map these quantitative traits to the genome, deriving loci underlying aspects of behavior.

Home-cage monitoring ascertains signatures of ictal and interictal behavior in mouse models of generalized seizures

“…Prior to PTZ exposure, DBA/2J mice displayed prominent home-cage hypoactivity compared with C57BL/6J, replicating findings from other home-cage platforms designed to measure activity or wheel-running only [27, 28, 62]. In our analysis, hypoactivity could not be explained by excess “sleep” but was associated with (or a result of) fewer but more prolonged feeding bouts.…”

“…While these tests are convenient and high throughput, they are short in duration (5–10 minutes long) and are often measured during the biological night (when lights are on). Virtually all of these tasks necessitate human presence/interference, which may directly impact reproducibility through inconsistent olfactory cues, variations in technique and bias [26, 27]. In this study, we employ an established home-cage monitoring platform [28, 29] to describe and appraise the acute severity of induced seizures as well as the severity of more pervasive changes in behavior that arise with recent seizures or with pervasively increased seizure risk (i.e., epilepsy).…”

Home-cage Monitoring Ascertains Signatures of Ictal and Interictal Behavior In Mouse Models of Generalized Seizures

“…Prior to PTZ exposure, DBA/2J mice displayed prominent home-cage hypoactivity compared with C57BL/6J, replicating prior findings (27,28,59). In our analysis, hypoactivity could not be explained by excess "sleep" but was associated with (or a result of) fewer but more prolonged feeding bouts.…”

“…While these tests are certainly convenient and offer a reasonably high throughput, they are short in duration (5-10 minutes long) and are often measured during the biological night (when lights are on). Virtually all of these tasks necessitate human presence/interference, which may directly impact reproducibility through inconsistent olfactory cues, variations in technique and bias (26,27).…”