Habituation of reflexive and motivated behavior in mice with deficient BK channel function

Abstract

Habituation is considered the most basic form of learning. It describes the decrease of a behavioral response to a repeated non-threatening sensory stimulus and therefore provides an important sensory filtering mechanism. While some neuronal pathways mediating habituation are well described, underlying cellular/molecular mechanisms are not yet fully understood. In general, there is an agreement that short-term and long-term habituation are based on different mechanisms. Historically, a distinction has also been made between habituation of motivated versus reflexive behavior. In recent studies in invertebrates the large conductance voltage- and calcium-activated potassium (BK) channel has been implicated to be a key player in habituation by regulating synaptic transmission. Here, we tested mice deficient for the pore forming α-subunit of the BK channel for short-term and long-term habituation of the acoustic startle reflex (reflexive behavior) and of the exploratory locomotor behavior in the open field box (motivated behavior). Short-term habituation of startle was completely abolished in the BK knock-out mice, whereas neither long-term habituation of startle nor habituation of motivated behavior was affected by the BK deficiency. Our results support a highly preserved mechanism for short-term habituation of startle across species that is distinct from long-term habituation mechanisms. It also supports the notion that there are different mechanisms underlying habituation of motivated behavior versus reflexive behavior.

A Genome-wide Screen Identifies PAPP-AA-Mediated IGFR Signaling as a Novel Regulator of Habituation Learning

“…With the exception of an unbiased, forward genetic screen for olfactory habituation mutants in Drosophila (Eddison et al, 2012; Wolf et al, 2007), only candidate gene approaches have been used to identify and dissect genetic mechanisms underlying habituation (Castro-Alamancos and Torres-Aleman, 1994; Das et al, 2011; Engel and Wu, 1998; Lau et al, 2012; Morrison and van der Kooy, 2001; Ohta et al, 2014; Rankin and Wicks, 2000; Rose et al, 2003; Sanyal et al, 2004; Swierczek et al, 2011; Typlt et al, 2013). To complement previous work and identify a broad set of core genes critical for vertebrate startle habituation, we conducted a classical three generation forward genetic screen.…”

The HIV-1 transgenic rat model of neuroHIV

“…The behavioral characteristics of short- and long-term habituation (Rankin, Abrams et al 2009) involve different neural and molecular mechanisms (Typlt, Mirkowski et al 2013). Although most studies of habituation focus on reflexive behaviors, such as orienting and startle responses, even motivated behaviors are modulated by habituation processes.…”

Verapamil Parameter- and Dose-Dependently Impairs Memory Consolidation in Open Field Habituation Task in Rats

“…In view of the fact that verapamil can block large conductance calcium-activated potassium channels (BK channel) (Harper et al, 2001) and that habituation of the exploratory locomotor behavior in the open field is not affected in the BK knock-out mice (Typlt et al, 2013), it could be less probable that the effect of verapamil be partially due to the action on these channels. It is possible that verapamil, through its action as an antagonist of P-glycoprotein transporters or multidrug resistance proteins (Pajeva and Wiese, 2002), impairs memory consolidation in open field task, since P-glycoprotein knockout mice display lower level of habituation than the wild-type mice (Schoenfelder et al, 2012).…”