α7 Nicotinic Receptor Subunits Are Not Necessary for Hippocampal-Dependent Learning or Sensorimotor Gating: A Behavioral Characterization of Acra7-Deficient Mice

Abstract

The α7 nicotinic acetylcholine receptor (nAChR) subunit is abundantly expressed in the hippocampus and contributes to hippocampal cholinergic synaptic transmission suggesting that it may contribute to learning and memory. There is also evidence for an association between levels of α7 nAChR and in sensorimotor gating impairments. To examine the role of α7 nAChRs in learning and memory and sensorimotor gating, Acra7 homozygous mutant mice and their wild-type littermates were tested in a Pavlovian conditioned fear test, for spatial learning in the Morris water task, and in the prepulse inhibition paradigm. Exploratory activity, motor coordination, and startle habituation were also evaluated. Acra7 mutant mice displayed the same levels of contextual and auditory-cue condition fear as wild-type mice. Similarly, there were no differences in spatial learning performance between mutant and wild-type mice. Finally,Acra7 mutant and wild-type mice displayed similar levels of prepulse inhibition. Other behavioral responses in Acra7 mutant mice were also normal, except for an anxiety-related behavior in the open-field test. The results of this study show that the absence of α7 nAChRs has little impact on normal, base-line behavioral responses. Future studies will examine the contribution of α7 nAChR to the enhancement of learning and sensorimotor gating following nicotine treatments.

Behavioral Phenotype of the Reeler Mutant Mouse: Effects of Reln Gene Dosage and Social Isolation.

“…Anxiety-related behavioral responses (Blaszczyk et al, 2001; Caston et al, 1999; Crabbe, Wahlsten, & Dudek, 1999; Crawley, 1999; Duncan, Knapp, & Breese, 1996; Fendt & Fanselow, 1999; Goldstein et al, 1994; Hascoet et al, 1999; Ishida-Tokuda et al, 1996; Lepicard et al, 2001; Maisonnette, Morato, & Brandao, 1993; Mathis, Neumann, Gershenfeld, Paul, & Crawley, 1995; Paylor et al, 1998; Smythe, Murphy, Timothy, & Costall, 1997; van Gaalen & Steckler, 2001) of +/rl mice appeared to be remarkably similar to wild-type ( +/+ ) control mice. They were indistinguishable in the numbers of fecal boli produced in open field, and they spent comparable proportions of time in the central portion of the open field arena.…”

“…After nose-poke testing, free feeding resumed, and 60 nose-poke-tested mice (a single, socially housed female rl/rl mouse was eliminated from testing during the nose-poke task) underwent a modified CER task (Crawley, 1999; Owen, Logue, Rasmussen, & Wehner, 1997; Paylor et al, 1998; Rondi-Reig et al, 1997; Schauz & Koch, 2001; van Gaalen & Steckler, 2001). The CER procedure required three trials of 6 min duration each, one trial per day.…”

“…When frightened, mice freeze (cease moving; Crawley, 1999; Fendt & Fanselow, 1999; Goldstein, Rasmusson, Bunney, & Roth, 1994; Huerta, Sun, Wilson, & Tonegawa, 2000; Ishida-Tokuda et al, 1996; Kalin, Shelton, Davidson, & Kelley, 2001; Owen et al, 1997; Paylor et al, 1998; Rampon et al, 2000; Rondi-Reig et al, 1997; Schauz & Koch, 2001; van Gaalen & Steckler, 2001). CER amplitude, the effectiveness of fear conditioning, was represented by the increased time spent without motion as measured for 40 s from the onset of the acoustic stimulus on Day 3 (after the sound-shock pairings on Day 2) relative to that following the neutral, novel acoustic stimulus on Day 1: (Day 3 freeze time − Day 1 freeze time)/Day 1 freeze time.…”

“…PPI. Assessment of PPI followed a modified version of procedures described by Bullock et al (1997); Dulawa, Hen, Scearce-Levie, and Geyer (1997);Geyer, Swerdlow, Mansbach, and Braff (1990); Kline, Decena, Hitzemann, and McCaughran (1998); Logue et al (1997); McCaughran, Mahjubi, Decena, and Hitzemann (1997); Paylor and Crawley (1997); Paylor et al (1998); Rothschild, O'Grady, and Wecker (1999); Sallinen, Haapalinna, Viitamaa, Kobilka, and Scheinin (1998); and Swerdlow and Geyer (1998). Following a 5-min acclimation period, individual subjects were presented 50 trials over a 12.39-min session.…”

Behavioral characterization of dopamine D₅ receptor null mutant mice.

“…Mice were first assessed on a simple screen designed to test for general health, gross behavioral abnormalities, and neurological reflexes (Crawley, 2000; Crawley & Paylor, 1997; Paylor et al, 1998). Body weight, piloerection, exophthalmos, and palpebral closure were measured and the presence of whiskers and bald patches was assessed.…”