The new field of “Computational Ethology” is made possible by advances in technology, mathematics, and engineering that allow scientists to automate the measurement and the analysis of animal ...behavior. We explore the opportunities and long-term directions of research in this area.
Since the 19th century, there has been disagreement over the fundamental question of whether “emotions” are cause or consequence of their associated behaviors. This question of causation is most ...directly addressable in genetically tractable model organisms, including invertebrates such as Drosophila. Yet there is ongoing debate about whether such species even have “emotions,” as emotions are typically defined with reference to human behavior and neuroanatomy. Here, we argue that emotional behaviors are a class of behaviors that express internal emotion states. These emotion states exhibit certain general functional and adaptive properties that apply across any specific human emotions like fear or anger, as well as across phylogeny. These general properties, which can be thought of as “emotion primitives,” can be modeled and studied in evolutionarily distant model organisms, allowing functional dissection of their mechanistic bases and tests of their causal relationships to behavior. More generally, our approach not only aims at better integration of such studies in model organisms with studies of emotion in humans, but also suggests a revision of how emotion should be operationalized within psychology and psychiatry.
Goal-directed social behaviours such as mating and fighting are associated with scalable and persistent internal states of emotion, motivation, arousal or drive. How those internal states are encoded ...and coupled to behavioural decision making and action selection is not clear. Recent studies in Drosophila melanogaster and mice have identified circuit nodes that have causal roles in the control of innate social behaviours. Remarkably, in both species, these relatively small groups of neurons can influence both aggression and mating, and also play a part in the encoding of internal states that promote these social behaviours. These similarities may be superficial and coincidental, or may reflect conserved or analogous neural circuit modules for the control of social behaviours in flies and mice.
Animals display a range of innate social behaviors that play essential roles in survival and reproduction. While the medial amygdala (MeA) has been implicated in prototypic social behaviors such as ...aggression, the circuit-level mechanisms controlling such behaviors are not well understood. Using cell-type-specific functional manipulations, we find that distinct neuronal populations in the MeA control different social and asocial behaviors. A GABAergic subpopulation promotes aggression and two other social behaviors, while neighboring glutamatergic neurons promote repetitive self-grooming, an asocial behavior. Moreover, this glutamatergic subpopulation inhibits social interactions independently of its effect to promote self-grooming, while the GABAergic subpopulation inhibits self-grooming, even in a nonsocial context. These data suggest that social versus repetitive asocial behaviors are controlled in an antagonistic manner by inhibitory versus excitatory amygdala subpopulations, respectively. These findings provide a framework for understanding circuit-level mechanisms underlying opponency between innate behaviors, with implications for their perturbation in psychiatric disorders.
Neurotropic viruses that conditionally infect or replicate in molecularly defined neuronal subpopulations, and then spread transsynaptically, are powerful tools for mapping neural pathways. ...Genetically targetable retrograde transsynaptic tracer viruses are available to map the inputs to specific neuronal subpopulations, but an analogous tool for mapping synaptic outputs is not yet available. Here we describe a Cre recombinase-dependent, anterograde transneuronal tracer, based on the H129 strain of herpes simplex virus (HSV). Application of this virus to transgenic or knockin mice expressing Cre in peripheral neurons of the olfactory epithelium or the retina reveals widespread, polysynaptic labeling of higher-order neurons in the olfactory and visual systems, respectively. Polysynaptic pathways were also labeled from cerebellar Purkinje cells. In each system, the pattern of labeling was consistent with classical circuit-tracing studies, restricted to neurons, and anterograde specific. These data provide proof-of-principle for a conditional, nondiluting anterograde transsynaptic tracer for mapping synaptic outputs from genetically marked neuronal subpopulations.
► A Cre-dependent, anterograde viral transynaptic tracer has been developed ► The tracer has been tested in the olfactory, visual, and cerebellar systems ► The pattern of labeling is consistent with classical studies and anterograde specific ► The tracer maps polysynaptic output pathways from genetically defined neuron subsets
The brain is worthy of study because it is in charge of behavior. A flurry of recent technical advances in measuring and quantifying naturalistic behaviors provide an important opportunity for ...advancing brain science. However, the problem of understanding unrestrained behavior in the context of neural recordings and manipulations remains unsolved, and developing approaches to addressing this challenge is critical. Here we discuss considerations in computational neuroethology—the science of quantifying naturalistic behaviors for understanding the brain—and propose strategies to evaluate progress. We point to open questions that require resolution and call upon the broader systems neuroscience community to further develop and leverage measures of naturalistic, unrestrained behavior, which will enable us to more effectively probe the richness and complexity of the brain.
The goal of computational neuroethology is to understand the relationship between the brain and purposive behavior that evolved under natural selection. Technology is transforming how we measure and model naturalistic behavior, affording new insight into brain function.
Males of most species are more aggressive than females, but the neural mechanisms underlying this dimorphism are not clear. Here, we identify a neuron and a gene that control the higher level of ...aggression characteristic of Drosophila melanogaster males. Males, but not females, contain a small cluster of FruM+ neurons that express the neuropeptide tachykinin (Tk). Activation and silencing of these neurons increased and decreased, respectively, intermale aggression without affecting male-female courtship behavior. Mutations in both Tk and a candidate receptor, Takr86C, suppressed the effect of neuronal activation, whereas overexpression of Tk potentiated it. Tk neuron activation overcame reduced aggressiveness caused by eliminating a variety of sensory or contextual cues, suggesting that it promotes aggressive arousal or motivation. Tachykinin/Substance P has been implicated in aggression in mammals, including humans. Thus, the higher aggressiveness of Drosophila males reflects the sexually dimorphic expression of a neuropeptide that controls agonistic behaviors across phylogeny.
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•A single class of neurons is identified that promotes aggression in male flies•These neurons are FruM+ and sexually dimorphic but do not control courtship•These neurons promote aggressive arousal via release of a neuropeptide, DTK•Tk is a neuropeptide gene that controls aggression in both flies and mammals
A small group of Drosophila neurons that are detectable in male, but not female, brains promote high levels of aggression via the release of a neuropeptide, Tachykinin. Homologs of this neuropeptide are implicated in mammalian aggression.
Pathological aggression and the inability to control aggressive impulses takes a tremendous toll on society. Yet aggression is a normal component of the innate behavior repertoire of most vertebrate ...animal species as well as of many invertebrates. Progress in understanding the etiology of disorders of aggressive behavior, whether genetic or environmental in nature, therefore requires an understanding of the brain circuitry that controls normal aggression. Efforts to understand this circuitry at the level of specific neuronal populations have been constrained by the limited resolution of classical methodologies, such as electrical stimulation and electrolytic lesion. The availability of new, genetically based tools for mapping and manipulating neural circuits at the level of specific, genetically defined neuronal subtypes provides an opportunity to investigate the functional organization of aggression circuitry with cellular resolution. However, these technologies are optimally applied in the mouse, where there has been surprisingly little traditional work on the functional neuroanatomy of aggression. Here we discuss recent, initial efforts to apply optogenetics and other state-of-the-art methods to the dissection of aggression circuitry in the mouse. We find, surprisingly, that neurons necessary and sufficient for inter-male aggression are located within the ventrolateral subdivision of the ventromedial hypothalamic nucleus, a structure traditionally associated with reproductive behavior. These neurons are intermingled with neurons activated during male–female mating, with approximately 20% overlap between the populations. We discuss the significance of these findings with respect to neuroethological and neuroanatomical perspectives on the functional organization of innate behaviors and their potential implications for psychiatry.
Mating and aggression are innate social behaviours that are controlled by subcortical circuits in the extended amygdala and hypothalamus
. The bed nucleus of the stria terminalis (BNSTpr) is a node ...that receives input encoding sex-specific olfactory cues from the medial amygdala
, and which in turn projects to hypothalamic nuclei that control mating
(medial preoptic area (MPOA)) and aggression
(ventromedial hypothalamus, ventrolateral subdivision (VMHvl)), respectively
. Previous studies have demonstrated that male aromatase-positive BNSTpr neurons are required for mounting and attack, and may identify conspecific sex according to their overall level of activity
. However, neural representations in BNSTpr, their function and their transformations in the hypothalamus have not been characterized. Here we performed calcium imaging
of male BNSTpr
neurons during social behaviours. We identify distinct populations of female- versus male-tuned neurons in BNSTpr, with the former outnumbering the latter by around two to one, similar to the medial amygdala and MPOA but opposite to VMHvl, in which male-tuned neurons predominate
. Chemogenetic silencing of BNSTpr
neurons while imaging MPOA
or VMHvl
neurons in behaving animals showed, unexpectedly, that the male-dominant sex-tuning bias in VMHvl was inverted to female-dominant whereas a switch from sniff- to mount-selective neurons during mating was attenuated in MPOA. Our data also indicate that BNSTpr
neurons are not essential for conspecific sex identification. Rather, they control the transition from appetitive to consummatory phases of male social behaviours by shaping sex- and behaviour-specific neural representations in the hypothalamus.
The extended amygdala has dominated research on the neural circuitry of fear and anxiety, but the septohippocampal axis also plays an important role. The lateral septum (LS) is thought to suppress ...fear and anxiety through its outputs to the hypothalamus. However, this structure has not yet been dissected using modern tools. The type 2 CRF receptor (Crfr2) marks a subset of LS neurons whose functional connectivity we have investigated using optogenetics. Crfr2+ cells include GABAergic projection neurons that connect with the anterior hypothalamus. Surprisingly, we find that these LS outputs enhance stress-induced behavioral measures of anxiety. Furthermore, transient activation of Crfr2+ neurons promotes, while inhibition suppresses, persistent anxious behaviors. LS Crfr2+ outputs also positively regulate circulating corticosteroid levels. These data identify a subset of LS projection neurons that promote, rather than suppress, stress-induced behavioral and endocrinological dimensions of persistent anxiety states and provide a cellular point of entry to LS circuitry.
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•Crfr2 defines a molecularly distinct subset of predominantly GABAergic LS neurons•Crfr2+ neuronal activation promotes, while inhibition suppresses, persistent anxiety•These anxiogenic effects are exerted in part via projections to medial hypothalamus•LS Crfr2+ outputs positively regulate circulating corticosteroid levels
Optogenetic circuit mapping identifies a population of neurons that send long-range projections from the lateral septum to the hypothalamus and enhance stress-induced anxiety behaviors that persist following transient neural activity. The findings provide new insights into the neural substrates of anxiety outside the amygdala and a cellular foothold on a little-explored brain area.
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