Serotonin, estrus, and social context influence c-Fos immunoreactivity in the inferior colliculus

Abstract

A fundamental task of sensory systems is to extract relevant social information from a range of environmental stimuli in the face of changing behavioral contexts and reproductive states. Neuromodulatory pathways that interact with such contextual variables are 1 mechanism for achieving this. In the mouse inferior colliculus (IC), a midbrain auditory region, the neuromodulator serotonin increases in females interacting with courting males, but events downstream of serotonin release have not been investigated. Here, we manipulated serotonin levels in female mice with the serotonin releaser fenfluramine or the serotonin depleter para-chlorophenylalaninemethyl ester (pCPA). Females were then exposed to an empty cage, a male partner, or a playback of courtship vocalizations, and the numbers of neurons in the IC with positive immunoreactivity for the immediate early gene product c-Fos were measured. The effects of drug treatments depended on social context and estrous state. Fenfluramine had greater effects in the nonsocial than in the partner social treatments. Females in proestrus or estrus and given fenfluramine had higher densities of c-Fos immunoreactive neurons, while females in diestrus had fewer immunoreactive neurons. The drug pCPA had the expected opposite effect of fenfluramine, causing a decreased response in pro/estrus females and an increased response in diestrus females. These findings show that the effects of serotonin on c-Fos activity in the IC of females is dependent on both external context and reproductive state, and suggest that these effects occur downstream of serotonin release. (PsycINFO Database Record

Figure 1

Control treatments prevent nuclear labeling by the c-fos antibody in the IC. A) No primary antibody control. B) No secondary control. C) 1:100 peptide block control. D) Regular c-fos labeling.

Figure 2

The average density of c-fos positive cells in females treated with either fenfluramine or saline (control). There was a significant interaction between drug and social treatment (univariate GLM: F = 5.663, p = 0.009). Inset shows the same data re-arranged to highlight differences among social groups. Bars represent standard error of the mean.

Figure 3

The proportional difference in the time spent performing locomotion, rearing, and digging in females in the playback vs. nonsocial groups. Females in the playback group displayed a large (3-fold) increase in digging behavior relative to the nonsocial group.

Figure 4

The average of the total duration of time females given either fenfluramine or a corresponding saline treatment spent performing locomotion, digging, and rearing. Fenfluramine significantly reduced activity (Mann-Whitney U, p < 0.001). Bars represent standard error of the mean.

Figure 5

The average of the total duration of time females given pCPA or a corresponding saline treatment spent performing locomotion, digging, and rearing. Females in the partner treatment group displayed lower levels of these behaviors (Kruskal-Wallis, p < 0.001). Bars represent standard error of the mean.

Figure 6

Relationship between the number of broadband vocalizations (BBVs) per interaction and c-fos immunoreactivity in the IC. A) The production of BBVs by females was negatively correlated with the density of c-fos positive cells in the IC cells (Spearman's ρ = −0.779, p = 0.002). B) Females listening to playbacks did not exhibit a correlation between BBVs and c-fos density (Spearman's ρ = −0.007, p = 0.983). Open circles represent saline treatment and closed circles represent pCPA treatment.

Figure 7

The average density of c-fos immunoreactive neurons in females either in diestrus or pro/estrus. A) Fenfluramine decreased c-fos immunoreactivity in diestrous females and increased c-fos immunoreactivity in estrous females (univariate GLM: Table 3). B) The treatment of pCPA increased c-fos immunoreactivity in diestrous females and decreased c-fos immunoreactivity in estrous females (univariate GLM: Table 3) Numbers of females are listed at the bottom of each bar. C) Among females represented in Fig. 7b there was a main effect of estrous state (univariate GLM: Table 3). Bars represent standard error of the mean.