Rats that learn to vocalize for food reward emit longer and louder appetitive calls and fewer short aversive calls.

Rats are social animals that use ultrasonic vocalizations (USV) in their intraspecific communication. Several types of USV have been previously described, e.g., appetitive 50-kHz USV and aversive short 22-kHz USV. It is not fully understood which aspects of the USV repertoire play important functions during rat ultrasonic exchange. Here, we investigated features of USV emitted by rats trained in operant conditioning, is a form of associative learning between behavior and its consequences, to reinforce the production/emission of 50-kHz USV. Twenty percent of the trained rats learned to vocalize to receive a reward according to an arbitrarily set criterion, i.e., reaching the maximum number of proper responses by the end of each of the last three USV-training sessions, as well as according to a set of measurements independent from the criterion (e.g., shortening of training sessions). Over the training days, these rats also exhibited: an increasing percentage of rewarded 50-kHz calls, lengthening and amplitude-increasing of 50-kHz calls, and decreasing number of short 22-kHz calls. As a result, the potentially learning rats, when compared to non-learning rats, displayed shorter training sessions and different USV structure, i.e. higher call rates, more rewarded 50-kHz calls, longer and louder 50-kHz calls and fewer short 22-kHz calls. Finally, we reviewed the current literature knowledge regarding different lengths of 50-kHz calls in different behavioral contexts, the potential function of short 22-kHz calls as well as speculate that USV may not easily become an operant response due to their primary biological role, i.e., communication of emotional state between conspecifics.

Spontaneously hypertensive rats manifest deficits in emotional response to 22-kHz and 50-kHz ultrasonic playback.

Many symptoms used routinely for human psychiatric diagnosis cannot be directly observed in animals which cannot describe their internal states. However, the ultrasonic vocalizations (USV) rodents use to communicate their emotional states can be measured. USV have therefore become a particularly useful tool in brain disease models. Spontaneously hypertensive rats (SHR) are considered an animal model of attention deficit hyperactivity disorder (ADHD) and schizophrenia. However, the specifics of SHR's behavior have not been fully described and there is very little data on their USV. Recently, we developed a communication model, in which Wistar rats are exposed to pre-recorded playbacks of aversive (22-kHz) or appetitive (50-kHz) USV, and their vocal responses depend on the extent of prior fear conditioning (0, 1, 6 or 10 shocks). Here, we investigated SHR's behavior and heart rate (HR) in our communication model, in comparison to Wistar rats employed as controls. In general, SHR emitted typical USV categories, however, they contained more short 22-kHz and less 50-kHz USV overall. Moreover, fewer SHR, in comparison with Wistar rats, emitted long 22-kHz USV after fear conditioning. SHR did not show a 50-kHz playback-induced HR increase, while they showed a profound 22-kHz playback-induced HR decrease. Finally, the number of previously delivered conditioning shocks appeared to have no effect on the investigated vocal, locomotor and HR responses of SHR. The phenomena observed in SHR are potentially attributable to deficits in emotional perception and processing. A lower number of 50-kHz USV emitted by SHR may reflect observations of speech impairments in human patients and further supports the usefulness of SHR to model ADHD and schizophrenia.

Activation of the 5-HT7 receptor and MMP-9 signaling module in the hippocampal CA1 region is necessary for the development of depressive-like behavior.

Major depressive disorder is a complex disease resulting from aberrant synaptic plasticity that may be caused by abnormal serotonergic signaling. Using a combination of behavioral, biochemical, and imaging methods, we analyze 5-HT7R/MMP-9 signaling and dendritic spine plasticity in the hippocampus in mice treated with the selective 5-HT7R agonist (LP-211) and in a model of chronic unpredictable stress (CUS)-induced depressive-like behavior. We show that acute 5-HT7R activation induces depressive-like behavior in mice in an MMP-9-dependent manner and that post mortem brain samples from human individuals with depression reveal increased MMP-9 enzymatic activity in the hippocampus. Both pharmacological activation of 5-HT7R and modulation of its downstream effectors as a result of CUS lead to dendritic spine elongation and decreased spine density in this region. Overall, the 5-HT7R/MMP-9 pathway is specifically activated in the CA1 subregion of the hippocampus during chronic stress and is crucial for inducing depressive-like behavior.

Increased Vocalization of Rats in Response to Ultrasonic Playback as a Sign of Hypervigilance Following Fear Conditioning.

We investigated the effects of prior stress on rats' responses to 50-kHz (appetitive) and 22-kHz (aversive) ultrasonic playback. Rats were treated with 0, 1, 6 or 10 shocks (1 s, 1.0 mA each) and were exposed to playbacks the following day. Previous findings were confirmed: (i) rats moved faster during 50-kHz playback and slowed down after 22-kHz playback; (ii) they all approached the speaker, which was more pronounced during and following 50-kHz playback than 22-kHz playback; (iii) 50-kHz playback caused heart rate (HR) increase; 22-kHz playback caused HR decrease; (iv) the rats vocalized more often during and following 50-kHz playback than 22-kHz playback. The previous shock affected the rats such that singly-shocked rats showed lower HR throughout the experiment and a smaller HR response to 50-kHz playback compared to controls and other shocked groups. Interestingly, all pre-shocked rats showed higher locomotor activity during 50-kHz playback and a more significant decrease in activity following 22-kHz playback; they vocalized more often, their ultrasonic vocalizations (USV) were longer and at a higher frequency than those of the control animals. These last two observations could point to hypervigilance, a symptom of post-traumatic stress disorder (PTSD) in human patients. Increased vocalization may be a valuable measure of hypervigilance used for PTSD modeling.