Trends in Neurosciences
ReviewBlueprints for behavior: genetic specification of neural circuitry for innate behaviors
Introduction
‘When, as by a miracle, the lovely butterfly bursts from the chrysalis full-winged and perfect,… it has, for the most part, nothing to learn, because its little life flows from its organization like melody from a music box.’ – Douglas A. Spalding (1873)
A major goal of neuroscience is to understand in molecular detail how neural circuits are built and subsequently function to permit individuals to perceive the world and carry out specific behaviors based on those perceptions. To gain insights into these issues, neuroscientists have generally either attempted to understand nervous system structure and function from studies of its elementary molecular and cellular components, or examined neural functions and behaviors in intact animals and attempted to relate these to large systems of neurons. Although both approaches have had many notable successes, it has not been clear how the knowledge collected at these two levels can be unified. Here, we focus on recent findings suggesting that developmental genetic and neurogenetic approaches to identifying the neural circuits underlying specific innate behaviors can bridge this gap.
The innate nature of many basic fixed action patterns and fairly invariant species-specific animal behaviors suggests that the underlying neuronal substrates necessary for their execution are genetically determined and developmentally programmed [1]. This makes innate behaviors particularly attractive systems for study, because genetic approaches can be exploited to address questions such as: What does it mean to ‘genetically program’ a behavior? And what are the elemental computations that behavioral circuits must execute? For example, how are innate behaviors elicited by specific environmental cues? How are sequential motor programs coordinated?
We begin with a brief summary of sex-developmental pathways in the regulation of Drosophila courtship, as background for recent work implicating transcription factors encoded by the fruitless (fru) gene as the crucial components that specify the neural substrates of Drosophila sexual behavior. We then discuss the implications of the findings that Fruitless-expressing neurons function at all levels of processing underlying this behavioral program. Based on these organizing principles, we briefly proceed to recent studies in vertebrates that implicate distinct genetically specified circuits – many of which operate through hypothalamic axes – in distinct programs for innate behaviors. Taking these findings together, we suggest that common principles govern the specification and organization of circuitry that underlies complex innate behavioral programs.
Section snippets
Male courtship behavior: the biological system
Sexual reproduction in many species is preceded by elaborate stereotyped courtship behaviors. In Drosophila courtship, the male engages in a series of actions including orienting towards and following the female, tapping her with his forelegs, singing a species-specific courtship song by vibrating one of his wings, licking the genitalia of the female, and curling his abdomen to attempt copulation 2, 3. Female behavior consists largely of avoidance and rejection. However, if unmated and
A circuit sufficient: from stimuli to behavior
One of the most significant findings from recent studies was that expression of male-specific FruM isoforms is sufficient to confer the potential for male courtship behavior in females 16, 19 (Figure 1). These experiments made use of the fact that P1 fru is transcribed in homologous cells in males and females but, because of post-transcriptional regulation, it normally produces FruM proteins only in males. Thus, it was possible to manipulate regulation of fru to produce FruM in females in cells
Functional analysis of FruM-expressing neurons
Recent studies have provided insights at two levels into the functional roles of FruM-expressing neurons. First, the findings that FruM-expressing neurons are generally present in small groups throughout the CNS and peripheral sensory system leads to the obvious prediction that groups of these neurons have distinct, specific roles in the reception, processing and transmission of information relevant to courtship or directing behaviors based on that information. Second, the observation that FruM
A role for P1 fru function in behavioral plasticity
In addition to beginning to characterize the contributions of specific populations of FruM-expressing neurons to distinct aspects of male sexual behaviors, Manoli et al. recently demonstrated that FruM expression in various components of the olfactory system is necessary for different experience-dependent modifications to male courtship [16]. Previous work had shown that, although naïve Drosophila males will initially court either male or female targets at first encounter, wild-type males
A dedicated circuit for sexual behaviors
Beyond the analysis of specific populations of FruM-expressing neurons and their contributions to sexual behaviors, investigation of whether FruM-expressing neurons are in fact dedicated to these programs has provided one of the most surprising findings regarding this circuitry: these neurons appear to be specifically dedicated to sexual behaviors. Transient inhibition of neurotransmission in only FruM-expressing cells demonstrated that these neurons function largely, if not exclusively, for
General principles for behavioral circuits
Based on the implications of these observations, we propose that for the circuitry specified for particular behavioral programs, distinct neuronal components must: (i) detect and integrate general and context-specific sensory information to identify distinct ethological contexts; (ii) relay such information to central components to determine specific behavioral states; (iii) coordinate and execute programs for behavioral sequences; and (iv) regulate basal elements of motor programs to generate
Similarities to vertebrate circuitry
It worth briefly considering three cases that demonstrate genetic regulation of behavioral circuitry in vertebrates. As discussed, if complex behavioral programs are maintained during evolution, it follows that the elements that regulate them are subject to tight genetic control and are likely to be linked to pathways that regulate the highest levels of development. In vertebrates, two developmental programs that regulate conserved and more basic developmental mechanisms throughout the organism
Neurogenetic approaches to behavioral circuits: blueprints for behaviors
Based on these principles governing genetically specified neural circuits, it is worth considering how further studies might best capitalize on the molecular and technical facility offered by genetically tractable model systems. The system afforded by fruitless represents a remarkable opportunity to explore the molecular, cellular and physiological basis for nervous system development and function, and more significantly how these functions transform information into action. As described,
Acknowledgements
We thank the members of the Baker laboratory for helpful comments and discussions. D.S.M. is supported by the MSTP Training Grant. G.W.M. and B.S.B. are supported by grants from the NIH.
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