Figure 2.
Distinct behavioral and neural adaptations to acute (1d) social defeat stress (1d-SDS) in wild-type (WT) and Lrrk2G2019S mice. (A) Schematic of the 1d-SDS paradigm followed by the social interaction (SI) test. In this paradigm, a WT or mutant C57Bl6 mouse is put into the home cage of a larger, CD1 retired male breeder. The larger CD1 aggressor physically subordinates the smaller C57Bl6 intruder for 5 minutes, then the two mice are separated for 15 minutes by a perforated divider, preventing further physical contact but maintaining the exchange of sensory cues. This process is repeated 2 more times on the same day, then the defeated mouse is returned to its home cage overnight. The next day, the mouse is subjected to an SI test, where the defeated mouse is allowed to explore an arena in the absence and subsequent presence of a novel social target constrained by a wire cage at one end of the arena. Video tracking monitors the amount of time the defeated mouse spends exploring the interaction zone with and without the social target present. (B) Heat maps showing movement of WT and Lrrk2G2019S mice during the SI test following 1d-SDS. Blue indicates path traveled; warmer colors indicate increased time. (C, D) Bar graphs/scatter plots showing time spent in the interaction zone during the SI test in the absence of a social target (C, P = 0.5478) and when the social target is present (D, P = 0.0117; WT, n = 13 mice; G2019S, n = 12 mice). Defeated mutant mice are significantly more socially avoidant in comparison with defeated WT mice. (E) Lrrk2G2019S mice show significantly greater sucrose consumption—a hedonic response—after 1d-SDS compared with 1d-SDS WT mice (P = 0.0432, WT, n = 7 mice; G2019S, n = 8 mice). (F) The intrinsic excitability of striatal projection neurons (SPNs) in the nucleus accumbens (NAc) is significantly elevated by 1d-SDS in WT mice—presumably an adaptive response to stress—but 1d-SDS does not alter intrinsic excitability of SPNs in Lrrk2G2019S mice. The input/output plot shows the number of action-potentials (spike number) elicited in response to depolarizing current steps applied to SPNs in the NAc. For each current step, defeated WT mice elicited more spikes in comparison with defeated G2019S mice or no-stress WT and G2019S control groups (at 140 pA: P = 0.0189; at 160 pA: P = 0.0115; at 180 pA: P = 0.0064; at 200 pA: P = 0.0095). Current step × genotype: F(42, 770) = 5.766, P < 0.001; main effect current step: F(2.307, 126.9) = 78.06, P < 0.001; main effect genotype: F(3, 55) = 8.658, P < 0.0001. (G) Representative traces of action potentials generated by current injection (180-pA step) into NAc SPNs taken from mice from each behavioral condition shown. All data are reproduced with permission from Guevara and others (2020).