*Review* **Biological Functions of Rat Ultrasonic Vocalizations, Arousal Mechanisms, and Call Initiation**

**Stefan M. Brudzynski**

**Citation:** Brudzynski, S.M. Biological Functions of Rat Ultrasonic Vocalizations, Arousal Mechanisms, and Call Initiation. *Brain Sci.* **2021**, *11*, 605. https://doi.org/10.3390/ brainsci11050605

Academic Editor: David Conversi

Received: 11 April 2021 Accepted: 5 May 2021 Published: 9 May 2021

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Department of Psychology, Brock University, St. Catharines, ON L2S 3A1, Canada; sbrudzynski@brocku.ca

**Abstract:** This review summarizes all reported and suspected functions of ultrasonic vocalizations in infant and adult rats. The review leads to the conclusion that all types of ultrasonic vocalizations subserving all functions are vocal expressions of emotional arousal initiated by the activity of the reticular core of the brainstem. The emotional arousal is dichotomic in nature and is initiated by two opposite-in-function ascending reticular systems that are separate from the cognitive reticular activating system. The mesolimbic cholinergic system initiates the aversive state of anxiety with concomitant emission of 22 kHz calls, while the mesolimbic dopaminergic system initiates the appetitive state of hedonia with concomitant emission of 50 kHz vocalizations. These two mutually exclusive arousal systems prepare the animal for two different behavioral outcomes. The transition from broadband infant isolation calls to the well-structured adult types of vocalizations is explained, and the social importance of adult rat vocal communication is emphasized. The association of 22 kHz and 50 kHz vocalizations with aversive and appetitive states, respectively, was utilized in numerous quantitatively measured preclinical models of physiological, psychological, neurological, neuropsychiatric, and neurodevelopmental investigations. The present review should help in understanding and the interpretation of these models in biomedical research.

**Keywords:** evolution of vocalization; ultrasonic vocalization; 22 kHz calls; 50 kHz calls; infant isolation calls; emotional arousal; mesolimbic dopaminergic system; mesolimbic cholinergic system; anxiety; hedonia; rat

#### **1. Introduction**

Production of vocalization is one of the best means of communication in most terrestrial vertebrates, even though many physical conditions and environmental objects influence and impede sound transmission. Vocal communication is not dependent on daylight and visibility or on the proximity of organisms, does not leave permanent traces, and in most situations, is not critically influenced by air currents, humidity, or temperature. It is, thus, not surprising that the emission of vocalization for intraspecies communication is one of the oldest features present in vertebrates and tetrapods, ranging from lung fish to humans [1–3]. The neuronal mechanisms for the regulation of fundamental features of vocalization, such as call duration and sound frequency, are located in the deep hindbrain, bordering the spinal cord [1,4]. They are conserved in the vertebrate evolution and could be demonstrated in species ranging from toadfishes, such as midshipmen fish [5], to mammals, such as rats [6]. Sound frequency and duration of vocalizations are regulated by separate hindbrain nuclei [5], which allow for the generation of a large number of combinations of sound parameters, and thus, the generation of different signals with different information content that still use the same acoustic mode of communication.

The old phylogenetic history of vocalizations suggests that the vocal form of communication is highly adaptive and has been biologically important for animal behavior for hundreds of millions of years (approx. 400 million years for tetrapods) [7]. In this review, the emphasis will be on rat vocalization, which is the most extensively studied in rodents. In addition, some other mammalian species will be mentioned because only mammals

have developed ventral myelinated vagal innervation, which originates from the nucleus ambiguous, innervates the larynx, and is critical for the generation of vocalization and the regulation of developed social interactions by the system termed social engagement system [8].

Studies of behavioral situations with the emission of ultrasonic vocalizations as indexes of emotional states have been extensively used as models of different neurodevelopmental, neurological, and psychiatric dysfunctions and diseases [9]. The magnitude and type of emitted ultrasonic calls were used in these models as a measure of the relevant effects. Therefore, there is a need for better understanding of the origin, nature, and role of rats' ultrasonic vocalizations, their initiation mechanisms, their interpretation, and their equivalence to human vocal emissions.

Rat ultrasonic calls cannot be compared with human speech because speech is only a human function, and rodents do not have the necessary neural mechanisms and developed cognitive brain to have this way of communication. However, rat ultrasonic calls may be compared with human vocalizations. This is a valid comparison because human non-verbal vocalizations, such as crying, laughing, grunting, groaning, moaning, or shrieking, do not have lexical content, are generated by subcortical limbic mechanisms, and are evolutionary counterparts of other mammalian vocalizations (for classification of human verbal and non-verbal vocalizations as well as pathological vocalizations, see [10]). Although animal vocalizations have many subtypes and may convey referential information or be situationspecific (e.g., in species of prairie dogs [11–13]), they do not represent language in a human sense and do not have grammatical structure, sentences, words, syllables, or even fully translatable meaning. Naming mammalian vocalizations as syllables, particularly those emitted in series, is a misnomer and mistake that is still repeated in the literature. Animal calls (and human vocalizations) remain simple signals, even though they may have some specific situational content or may be emitted repeatedly or in a combination of calls. Vocalizations represent an evolutionarily older system of communication than human language with different neural regulation and different semiosis ("meaning"), and these two types of vocal communication should not be confused. Moreover, animal vocalizations were suggested to be interpreted as means of influencing the behavior of other individuals in a general way, rather than signals sending specific (e.g., lexical type) information to conspecifics as we know it from human language [14].

This review will attempt to facilitate understanding of functions of rat vocalizations, i.e., answering the question of why rats emit their calls. Different functions of vocalizations reflect our understanding of situations favoring vocal communication, and they do not mean that animals have many "understandings" or many intentional scenarios of call emission. Moreover, the emission of ultrasonic calls may serve more than one function at the same time. Thus, the classification of the functions of emitted vocalizations is used as a heuristic tool for the classification of the behavioral roles that vocalizations play in phylogenetic and ontogenetic history. Such a classification of documented or suspected functions of rat ultrasonic vocalizations has not yet been fully accomplished [15–18], and it will aid the ultimate goal of this review, which is to cumulate evidence supporting the hypothesis that all types of rat vocalizations, serving all biological functions, are driven by emotional arousal. Neural mechanisms that initiate emotional arousal, positive or negative, are, therefore, common in fulfilling any of these functions.

#### **2. Evolution and Functions of Rat Vocalizations**
