Differential Release of Acetylcholine and Dopamine in the Basolateral Amygdala Shapes Behavioral Responses to Emotional Vocalizations in Mice

Core Concepts

Distinct patterns of acetylcholine and dopamine release in the basolateral amygdala modulate behavioral responses to emotionally salient vocalizations in male and female mice, depending on their prior experience and hormonal state.

Abstract

This study investigates how the release of neuromodulators, specifically acetylcholine (ACh) and dopamine (DA), in the basolateral amygdala (BLA) contributes to the processing of emotionally salient vocalizations and the resulting behavioral responses in male and female mice. The key findings are: Playback of vocalizations associated with mating or restraint behaviors elicited distinct patterns of ACh and DA release in the BLA of male mice. Restraint vocalizations increased ACh release and decreased DA release, while mating vocalizations had the opposite effect. In female mice, the estrous stage modulated the ACh response to mating vocalizations. Estrus females showed increased ACh release, which was associated with increased vigilance behaviors like flinching, compared to non-estrus females and males. A single prior experience with mating or restraint behaviors was sufficient to shape the neurochemical and behavioral responses to the corresponding vocal stimuli. Mice without this prior experience did not exhibit the distinct patterns of ACh and DA release observed in experienced animals. The results suggest that ACh and DA provide context- and state-dependent information to BLA neurons during the processing of emotionally salient vocalizations, which in turn modulates the behavioral responses of the listener. This highlights the importance of neuromodulatory inputs in shaping how the amygdala processes and responds to social communication signals.

Stats

Restraint vocalizations increased ACh release in the BLA of male mice by 24% and 25% during the two 10-min playback periods, respectively, compared to baseline. Mating vocalizations decreased ACh release in the BLA of male mice by 19% and 16.4% during the two 10-min playback periods, respectively, compared to baseline. Mating vocalizations increased DA release in the BLA of male mice by 12% and 25% during the two 10-min playback periods, respectively, compared to baseline. Restraint vocalizations decreased DA release in the BLA of male mice by 11% and 22% during the two 10-min playback periods, respectively, compared to baseline. Estrus female mice showed a 29.3% and 25.5% increase in ACh release in the BLA during the two 10-min playback periods of mating vocalizations, compared to a decrease in males and non-estrus females.

Quotes

"Distinct patterns of ACh and DA release into the BLA depending on the type of vocalization playback." "Estrus females showed increased ACh release, which was associated with increased vigilance behaviors like flinching, compared to non-estrus females and males." "A single prior experience with mating or restraint behaviors was sufficient to shape the neurochemical and behavioral responses to the corresponding vocal stimuli."

Key Insights Distilled From

Emotional Vocalizations Alter Behaviors and Neurochemical Release into the Amygdala

by Ghasemahmad,... at www.biorxiv.org 07-04-2022

https://www.biorxiv.org/content/10.1101/2022.07.02.498564v5

Deeper Inquiries

How do the experience-dependent changes in ACh and DA release in the BLA translate into long-term modifications of vocal processing and social behavior

Experience-dependent changes in acetylcholine (ACh) and dopamine (DA) release in the basolateral amygdala (BLA) play a crucial role in shaping long-term modifications of vocal processing and social behavior. The BLA is a key brain region involved in emotional processing and behavioral responses to salient stimuli, including vocalizations. The release of ACh and DA in the BLA provides contextual information during the processing of affective vocalizations, influencing the activity of BLA neurons and modulating downstream brain regions controlling behavioral responses. Through experience-dependent changes in ACh and DA release, the BLA undergoes plasticity and forms associations between specific vocal cues and behavioral responses. For example, repeated exposure to mating or restraint experiences leads to consistent patterns of ACh and DA release in response to corresponding vocalizations. These neuromodulatory changes can strengthen the synaptic connections and neural circuits involved in processing these vocal cues, leading to long-term modifications in vocal processing and social behavior. The balance between ACh and DA release in the BLA shapes the valence and salience of vocal cues, influencing the animal's emotional responses and social interactions over time.

What are the specific neural circuit mechanisms by which ACh and DA modulate the activity of BLA projection neurons that control appetitive versus aversive behavioral responses to vocalizations

The specific neural circuit mechanisms by which acetylcholine (ACh) and dopamine (DA) modulate the activity of basolateral amygdala (BLA) projection neurons that control appetitive versus aversive behavioral responses to vocalizations involve complex interactions between neuromodulators, neurons, and downstream brain regions. In the BLA, ACh and DA act on different receptor subtypes to modulate the activity of projection neurons. ACh, released from cholinergic projections originating in the basal forebrain, can enhance the excitatory responses of BLA neurons through muscarinic ACh receptors (mAChRs). This modulation can lead to persistent firing and sharpen the signal-to-noise ratio in response to aversive cues. On the other hand, DA released from the ventral tegmental area (VTA) acts on D1 and D2 receptors in BLA neurons. DA enhances the activity of reward-responding neurons through D2 receptors, while suppressing the activity of aversive-responding neurons via D1 receptors. The interaction between ACh and DA in the BLA helps to regulate the balance between appetitive and aversive behavioral responses to vocalizations. ACh and DA play complementary roles in shaping the neural circuits involved in processing emotional cues, influencing the output of BLA projection neurons to downstream brain regions such as the nucleus accumbens and central nucleus of the amygdala.

Could the differential release of ACh and DA in the BLA during vocal processing be leveraged as a biomarker for assessing emotional and social deficits in animal models of neuropsychiatric disorders

The differential release of acetylcholine (ACh) and dopamine (DA) in the basolateral amygdala (BLA) during vocal processing could potentially serve as a biomarker for assessing emotional and social deficits in animal models of neuropsychiatric disorders. In neuropsychiatric disorders characterized by altered emotional processing and social behavior, dysregulation of ACh and DA systems in the BLA may contribute to the manifestation of symptoms. By measuring the patterns of ACh and DA release in response to vocalizations, researchers can gain insights into the neural mechanisms underlying these disorders and identify potential biomarkers for assessing emotional and social deficits. For example, abnormalities in ACh release in the BLA, such as heightened or reduced levels in response to specific vocal cues, could indicate dysfunction in emotional processing and behavioral responses. Similarly, alterations in DA release patterns, such as imbalances between D1 and D2 receptor activation, may be indicative of deficits in reward processing and aversive responses. By leveraging the differential release of ACh and DA in the BLA as biomarkers, researchers can better understand the neurobiological basis of neuropsychiatric disorders and develop targeted interventions to modulate these neuromodulatory systems for therapeutic purposes.