Extinction and Retrieval + Extinction of Conditioned Fear Differentially Activate Medial Prefrontal Cortex and Amygdala in Rats

Pairing a previously neutral conditioned stimulus (CS; e.g., a tone) to an aversive unconditioned stimulus (US; e.g., a footshock) leads to associative learning such that the tone alone comes to elicit a conditioned response (e.g., freezing). We have previously shown that an extinction session that occurs within the reconsolidation window (termed retrieval+extinction) attenuates fear responding and prevents the return of fear in Pavlovian fear conditioning (Monfils et al., 2009). To date, the mechanisms that explain the different behavioral outcomes between standard extinction and retrieval+extinction remain poorly understood. Here we sought to examine the differential temporal engagement of specific neural systems by these 2 approaches using Arc catFISH (cellular compartment analysis of temporal activity using fluorescence in situ hybridization). Our results demonstrate that extinction and retrieval+extinction lead to differential patterns of expression, suggesting that they engage different networks. These findings provide insight into the neural mechanisms that allow extinction during reconsolidation to prevent the return of fear in rats

Strain and sex differences in fear conditioning: 22 kHz ultrasonic vocalizations and freezing in rats

Abstract Strain and sex differences in fear conditioning were investigated in two commonly used laboratory rats: Sprague Dawleys and Long-Evans. Twenty-two kHz ultrasonic vocalization (USV) distress calls and freezing behavior were used to measure fear responses to contextual and auditory conditioned stimuli (CSs), which were previously paired with a footshock unconditioned stimulus (US). Both strain and sex had significant effects on USVs and freezing during training and subsequent context and tone tests. Overall, the male Sprague Dawley rats froze and emitted USVs more than the other groups. Additionally, levels of freezing and USVs were differentially influenced by the type of CS (context or tone). These results suggest that species-specific defense responses in laboratory rats are highly influenced by the strain and sex of the subject, and that these factors should be considered in future fear conditioning studies

Friend recollections, and a collection of collaborations with Nadia

In this selective review article, we showcase our collaborations with our colleague, Dr. Nadia Chaudhri. Dr. Chaudhri was an esteemed colleague and researcher who contributed greatly to our understanding of Pavlovian alcohol conditioning. From 2014 to 2019, we collaborated with Nadia. Here, we reflect on our friendship, the work we did together, and the continued impact on the field

Cue-alcohol associative learning in female rats

The ability of environmental cues to trigger alcohol seeking behaviors is believed to facilitate problematic alcohol use. We previously showed that the development of this cue-evoked alcohol approach reflects cue-alcohol learning and memory in the adult male rat; however, we do not know whether the same is true for similarly aged female rats. Consequently, adult Long-Evans female rats were allowed to drink unsweetened alcohol in the homecage (MWF 24 hr two-bottle choice, 5 weeks) and subsequently split into two experimental groups: paired and unpaired. Groups were matched for ingested doses and alcohol bottle preference across the pre-conditioning homecage period. Both groups were trained in conditioning chambers using a Pavlovian procedure. For the paired group, the chamber houselight was illuminated to signal access to an alcohol sipper. Houselight onset was yoked for the unpaired group, but access to the alcohol sipper was scheduled to occur only during the intervening periods (in the absence of light). We found that in the paired, but not unpaired group, an alcohol approach reaction was conditioned to houselight illumination, and the level of cue-conditioned reactivity predicted drinking behavior within trials. Groups experienced equivalently low but non-negligible blood alcohol concentrations over the course of conditioning sessions. We conclude that cue-triggered alcohol seeking behavior in adult female rats reflects associative learning about the relationship between alcohol availability and houselight illumination

Alcohol-associated antecedent stimuli elicit alcohol seeking in non-dependent rats and may activate the insula

Alcohol self-administration produces brain and behavior adaptations that facilitate a progressive loss of control over drinking and contribute to relapse. One possible adaptation is the ability of antecedent environmental stimuli that are consistently paired with alcohol to trigger alcohol seeking behaviors. We previously modeled this adaptation in rats using a Pavlovian conditioning procedure in which illumination of a houselight preceded the presentation of a sipper tube that produced unsweetened alcohol when licked. However, in our previous work we did not demonstrate whether this adaptation represented a consequence of repeated exposure to alcohol or the houselight, or whether it was the consequence of associative learning and memory. Thus, in the present study, we tested the associative basis of alcohol seeking in response to houselight illumination in our task using adult male rats that were not food or water deprived and were not dependent on alcohol. Separate groups of rats received houselight illumination that was explicitly paired or unpaired with presentation of the retractable sipper that provided access to unsweetened alcohol. Our primary dependent variable was appetitive alcohol-directed behavior: the frequency of movement toward and interaction with the hole in the wall of the chamber through which the sipper was presented during the period of houselight illumination trial before each sipper presentation. However, we also analyzed consummatory sipper licking behavior and blood ethanol concentration in the same rats. Finally, we explored the brain basis of cue-elicited alcohol seeking using c-Fos immunohistochemistry. Our findings confirmed the associative basis of cue-elicited alcohol seeking in our paradigm and mapped these onto the insular cortex, suggesting a role for this brain region in early stages of brain and behavior adaptation to regular alcohol us