Auditory Cortex is Important in the Extinction of Two Different Tone-Based Conditioned Fear Memories in Rats

Extensive fear extinction research is guided by the view that there are structures in the brain that develop inhibitory control over the expression of conditioned fear memories. While the medial prefrontal cortex has recently captured attention as the locus of plasticity essential for extinction of conditioned fear, the auditory cortex is another plausible cortical area involved in extinction learning since it is considered a sufficient conditioned stimulus (CS) pathway in tone fear conditioning. We examined the role of auditory cortex in extinction of auditory-based fear memories with a standard tone-on conditioning, wherein a tone CS predicted a footshock unconditioned stimulus (US), or a novel tone-off conditioning, in which the tone was continually present and the offset of the tone was the CS predicting the US. Rats with bilateral auditory cortex lesions were trained in either paradigm and subsequently trained in extinction to the CS. Auditory cortex lesions had no effect on acquisition but impaired extinction to both CSs. These findings indicate that the auditory cortex contributes to extinction of wide-ranging auditory fear memories, as evidenced by deficits in both tone-on CS and tone-off CS extinction training

Neuroethological studies of fear, anxiety, and risky decision-making in rodents and humans

Prey are relentlessly faced with a series of survival problems to solve. One enduring problem is predation, where the prey's answers rely on the complex interaction between actions cultivated during its life course and defense reactions passed down by descendants. To understand the proximate neural responses to analogous threats, affective neuroscientists have favored well-controlled associative learning paradigms, yet researchers are now creating semi-realistic environments that examine the dynamic flow of decision-making and escape calculations that mimic the prey's real world choices. In the context of research from the field of ethology and behavioral ecology, we review some of the recent literature in rodent and human neuroscience and discuss how these studies have the potential to provide new insights into the behavioral expression, computations, and the neural circuits that underlie healthy and pathological fear and anxiety

Stress impairs decision-making in rats

Stress influences various types of memory, but its effects on other cognitive functions are relatively unknown. We investigated the effects of uncontrollable stress on subsequent decision-making in rats, using a computer vision-based water foraging choice task. Stress impaired the animals' ability to bias their responses toward the larger reward when transitioning from equal to unequal quantities, and this stress effect was dependent on the amygdala

Neuroethological studies of fear, anxiety, and risky decision-making in rodents and humans

Prey are relentlessly faced with a series of survival problems to solve. One enduring problem is predation, where the prey's answers rely on the complex interaction between actions cultivated during its life course and defense reactions passed down by descendants. To understand the proximate neural responses to analogous threats, affective neuroscientists have favored well-controlled associative learning paradigms, yet researchers are now creating semi-realistic environments that examine the dynamic flow of decision-making and escape calculations that mimic the prey's real world choices. In the context of research from the field of ethology and behavioral ecology, we review some of the recent literature in rodent and human neuroscience and discuss how these studies have the potential to provide new insights into the behavioral expression, computations, and the neural circuits that underlie healthy and pathological fear and anxiety

Social Transmission of Fear in Rats: The Role of 22-kHz Ultrasonic Distress Vocalization

Background: Social alarm calls alert animals to potential danger and thereby promote group survival. Adult laboratory rats in distress emit 22-kHz ultrasonic vocalization (USV) calls, but the question of whether these USV calls directly elicit defensive behavior in conspecifics is unresolved. Methodology/Principal Findings: The present study investigated, in pair-housed male rats, whether and how the conditioned fear-induced 22-kHz USVs emitted by the ‘sender ’ animal affect the behavior of its partner, the ‘receiver ’ animal, when both are placed together in a novel chamber. The sender rats ’ conditioned fear responses evoked significant freezing (an overt evidence of fear) in receiver rats that had previously experienced an aversive event but not in naïve receiver rats. Permanent lesions and reversible inactivations of the medial geniculate nucleus (MGN) of the thalamus effectively blocked the receivers ’ freeezing response to the senders ’ conditioned fear responses, and this occurred in absence of lesions/ inactivations impeding the receiver animals ’ ability to freeze and emit 22-kHz USVs to the aversive event per se. Conclusions/Significance: These results—that prior experience of fear and intact auditory system are required for receiver rats to respond to their conspecifics ’ conditioned fear responses—indicate that the 22-kHz USV is the main factor for socia

Functional Imaging of Stimulus Convergence in Amygdalar Neurons during Pavlovian Fear Conditioning

Background: Associative conditioning is a ubiquitous form of learning throughout the animal kingdom and fear conditioning is one of the most widely researched models for studying its neurobiological basis. Fear conditioning is also considered a model system for understanding phobias and anxiety disorders. A fundamental issue in fear conditioning regards the existence and location of neurons in the brain that receive convergent information about the conditioned stimulus (CS) and unconditioned stimulus (US) during the acquisition of conditioned fear memory. Convergent activation of neurons is generally viewed as a key event for fear learning, yet there has been almost no direct evidence of this critical event in the mammalian brain. Methodology/Principal Findings: Here, we used Arc cellular compartmental analysis of temporal gene transcription by fluorescence in situ hybridization (catFISH) to identify neurons activated during single trial contextual fear conditioning in rats. To conform to temporal requirements of catFISH analysis we used a novel delayed contextual fear conditioning protocol which yields significant single- trial fear conditioning with temporal parameters amenable to catFISH analysis. Analysis yielded clear evidence that a population of BLA neurons receives convergent CS and US information at the time of the learning, that this only occurs when the CS-US arrangement is supportive of the learning, and that this process requires N-methyl-D-aspartate receptor activation. In contrast, CS-US convergence was not observed in dorsal hippocampus

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

Selective enhancement of emotional, but not motor, learning in monoamine oxidase A-deficient mice

Mice deficient in monoamine oxidase A (MAOA), an enzyme that metabolizes monoamines such as norepinephrine and serotonin, have elevated norepinephrine and serotonin levels in the frontal cortex, hippocampus, and cerebellum, compared with normal wild-type mice. Since monoamines in these areas are critically involved in a variety of behaviors, we examined learning and memory (using emotional and motor tasks) in MAOA mutant mice. The MAOA-deficient mice exhibited significantly enhanced classical fear conditioning (freezing to both tone and contextual stimuli) and step-down inhibitory avoidance learning. In contrast, eyeblink conditioning was normal in these mutant mice. The female MAOA-deficient mice also displayed normal species-typical maternal behaviors (nesting, nursing, and pup retrieval). These results suggest that chronic elevations of monoamines, due to a deletion of the gene encoding MAOA, lead to selective alterations in emotional behavior.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56225/1/kimPNAS97.pd