Behavioral Neuroscience publications

Survival relies on an organism's intrinsic ability to instinctively react to stimuli such as food, water, and threats, ensuring the fundamental ability to feed, drink, and avoid danger even in the absence of prior experience. These natural, unconditioned stimuli can also facilitate associative learning, where pairing them consistently with neutral cues will elicit responses to these cues. Threat conditioning, a well-explored form of associative learning, commonly employs painful electric shocks, mimicking injury, as unconditioned stimuli. It remains elusive whether actual injury or pain is necessary for effective learning, or whether the threat of harm is sufficient. Approaching predators create looming shadows and sounds, triggering strong innate defensive responses like escape and freezing. This study investigates whether visual looming stimuli can induce learned freezing or learned escape responses to a conditioned stimulus in male rats. Surprisingly, pairing a neutral tone with a looming stimulus only weakly evokes learned defensive responses, in contrast to the strong responses observed when the looming stimulus is replaced by a shock. This dissociation sheds light on the boundaries for learned defensive responses thereby impacting our comprehension of learning processes and defensive strategies.

Anticipating positive outcomes is a core cognitive function in the process of reward prediction. However, no neurophysiological method objectively assesses reward prediction in basic medical research. In the present study, we established a physiological paradigm using cortical direct current (DC) potential responses in rats to assess reward prediction. This paradigm consisted of five daily 1-h sessions with two tones, wherein the rewarded tone was followed by electrical stimulation of the medial forebrain bundle (MFB) scheduled at 1000 ms later, whereas the unrewarded tone was not. On day 1, both tones induced a negative DC shift immediately after auditory responses, persisting up to MFB stimulation. This negative shift progressively increased and peaked on day 4. Starting from day 3, the negative shift from 600 to 1000 ms was significantly larger following the rewarded tone than that following the unrewarded tone. This negative DC shift was particularly prominent in the frontal cortex, suggesting its crucial role in discriminative reward prediction. During the extinction sessions, the shift diminished significantly on extinction day 1. These findings suggest that cortical DC potential is related to reward prediction and could be a valuable tool for evaluating animal models of depression, providing a testing system for anhedonia.

Animals use auditory cues generated by defensive responses of others to detect impending danger. Here we identify a neural circuit in rats involved in the detection of one such auditory cue, the cessation of movement-evoked sound resulting from freezing. This circuit comprises the dorsal subnucleus of the medial geniculate body (MGD) and downstream areas, the ventral area of the auditory cortex (VA), and the lateral amygdala (LA). This study suggests a role for the auditory offset pathway in processing a natural sound cue of threat.

The ability to recognize sounds in noise is a key part of hearing, and the mechanisms by which the brain identifies sounds in noise are of considerable interest to scientists, clinicians and engineers. Yet we know little about the necessity of regions such as auditory cortex for hearing in noise, or how cortical processing of sounds is adversely affected by noise. Here we used reversible cortical inactivation and extracellular electrophysiology in ferrets performing a vowel discrimination task to identify and understand the causal contribution of auditory cortex to hearing in noise. Cortical inactivation by cooling impaired task performance in noisy but not clean conditions, while responses of auditory cortical neurons were less informative about vowel identity in noise. Simulations mimicking cortical inactivation indicated that effects of inactivation were related to the loss of information about sounds represented across neural populations. The addition of noise to target sounds drove spiking activity in auditory cortex and recruitment of additional neural populations that were linked to degraded behavioral performance. To suppress noise-related activity, we used continuous exposure to background noise to adapt the auditory system and recover behavioral performance in both ferrets and humans. Inactivation by cooling revealed that the benefits of continuous exposure were not cortically dependent. Together our results highlight the importance of auditory cortex in sound discrimination in noise and the underlying mechanisms through which noise-related activity and adaptation shape hearing.

Social cues of threat are widely reported [1–3], whether actively produced to trigger responses in others, such as the emission of alarm calls, or by-products of an encounter with a predator, like the defensive behaviors themselves, such as an escape flight [4–14]. Although the recognition of social alarm cues is often innate [15–17], in some instances it requires experience to trigger defensive responses [4,7]. One mechanism proposed for how learning from self-experience contributes to social behavior is that of auto-conditioning, whereby subjects learn to associate their own behaviors with the relevant trigger events. Through this process the same behaviors, now displayed by others, gain meaning. [18,19 but see: 20]. Although it has been shown that only animals with prior experience with shock display observational freezing [21–25] suggesting that auto-conditioning could mediate this process, evidence for this hypothesis was lacking. Previously we found that when a rat freezes, the silence that results from immobility triggers observational freezing in its cage-mate, provided the cage-mate had experienced shocks before [24]. Hence, in our study auto-conditioning would correspond to rats learning to associate shock with their own response to it – freezing. Using a combination of behavioral and optogenetic manipulations, here we show that freezing becomes an alarm cue by a direct association with shock. Our work shows that auto-conditioning can indeed modulate social interactions, expanding the repertoire of cues that mediate social information exchange, providing a framework to study how the neural circuits involved in the self-experience of defensive behaviors overlap with the ones involved in socially triggered defensive behaviors.

Animal models are widely used to examine the neurophysiological basis of human pitch perception, and it is therefore important to understand the similarities and differences in pitch processing across species. Pitch discrimination performance is usually measured using two-alternative forced choice (2AFC) procedures in humans and go/no-go tasks in animals, potentially confounding human-to-animal comparisons. We have previously shown that pitch discrimination thresholds of ferrets on a 2AFC task are markedly poorer than those reported for go/no-go tasks in other non-human species (Walker et al ., 2009). To better compare the pitch discrimination performance of ferret with other species, here we measure pitch change detection thresholds of ferrets and humans on a common, appetitive go/no-go task design. We found that ferrets’ pitch thresholds were ~10 times larger than that of humans on the go/no-go task, and were within the range of thresholds reported in other non-human species. Interestingly, ferrets’ thresholds were 100 times larger than human thresholds on a 2AFC pitch discrimination task using the same stimuli. These results emphasize that sensory discrimination thresholds can differ across tasks, particularly for non-human animals. Performance on our go/no-go task is likely to reflect different neurobiological processes than that on our 2AFC task, as the former required the subjects only to detect a pitch change while the latter required them to label the direction of the pitch change. ABBREVIATIONS 2AFC 2-Alternative Forced Choice F0 Fundamental Frequency HIGHLIGHTS Pitch discrimination thresholds of ferrets were 10 times larger than those of humans on a go/no-go task Ferrets’ pitch thresholds are similar to those reported for a range of other mammals Pitch thresholds of ferrets, but not humans, were drastically better on the go/no-go task than a 2AFC task using the same stimuli

Ultimately associative learning is a function of the temporal features and relationships between experienced stimuli. Nevertheless how time affects the neural circuit underlying this form of learning remains largely unknown. To address this issue, we used single-trial auditory trace fear conditioning and varied the length of the interval between tone and foot-shock. Through temporary inactivation of the amygdala, medial prefrontal-cortex (mPFC), and dorsal-hippocampus in rats, we tested the hypothesis that different temporal intervals between the tone and the shock influence the neuronal structures necessary for learning. With this study we provide the first experimental evidence showing that temporarily inactivating the amygdala before training impairs auditory fear learning when there is a temporal gap between the tone and the shock. Moreover, imposing a short interval (5 s) between the two stimuli also relies on the mPFC, while learning the association across a longer interval (40 s) becomes additionally dependent on a third structure, the dorsal-hippocampus. Thus, our results suggest that increasing the interval length between tone and shock leads to the involvement of an increasing number of brain areas in order for the association between the two stimuli to be acquired normally. These findings demonstrate that the temporal relationship between events is a key factor in determining the neuronal mechanisms underlying associative fear learning.