The malleable brain: plasticity of neural circuits and behavior: A review from students to students

One of the most intriguing features of the brain is its ability to be malleable, allowing it to adapt continually to changes in the environment. Specific neuronal activity patterns drive long-lasting increases or decreases in the strength of synaptic connections, referred to as long-term potentiation (LTP) and long-term depression (LTD) respectively. Such phenomena have been described in a variety of model organisms, which are used to study molecular, structural, and functional aspects of synaptic plasticity. This review originated from the first International Society for Neurochemistry (ISN) and Journal of Neurochemistry (JNC) Flagship School held in Alpbach, Austria (Sep 2016), and will use its curriculum and discussions as a framework to review some of the current knowledge in the field of synaptic plasticity. First, we describe the role of plasticity during development and the persistent changes of neural circuitry occurring when sensory input is altered during critical developmental stages. We then outline the signaling cascades resulting in the synthesis of new plasticity-related proteins, which ultimately enable sustained changes in synaptic strength. Going beyond the traditional understanding of synaptic plasticity conceptualized by LTP and LTD, we discuss system-wide modifications and recently unveiled homeostatic mechanisms, such as synaptic scaling. Finally, we describe the neural circuits and synaptic plasticity mechanisms driving associative memory and motor learning. Evidence summarized in this review provides a current view of synaptic plasticity in its various forms, offers new insights into the underlying mechanisms and behavioral relevance, and provides directions for future research in the field of synaptic plasticity.Fil: Schaefer, Natascha. University of Wuerzburg; AlemaniaFil: Rotermund, Carola. University of Tuebingen; AlemaniaFil: Blumrich, Eva Maria. Universitat Bremen; AlemaniaFil: Lourenco, Mychael V.. Universidade Federal do Rio de Janeiro; BrasilFil: Joshi, Pooja. Robert Debre Hospital; FranciaFil: Hegemann, Regina U.. University of Otago; Nueva ZelandaFil: Jamwal, Sumit. ISF College of Pharmacy; IndiaFil: Ali, Nilufar. Augusta University; Estados UnidosFil: García Romero, Ezra Michelet. Universidad Veracruzana; MéxicoFil: Sharma, Sorabh. Birla Institute of Technology and Science; IndiaFil: Ghosh, Shampa. Indian Council of Medical Research; IndiaFil: Sinha, Jitendra K.. Indian Council of Medical Research; IndiaFil: Loke, Hannah. Hudson Institute of Medical Research; AustraliaFil: Jain, Vishal. Defence Institute of Physiology and Allied Sciences; IndiaFil: Lepeta, Katarzyna. Polish Academy of Sciences; ArgentinaFil: Salamian, Ahmad. Polish Academy of Sciences; ArgentinaFil: Sharma, Mahima. Polish Academy of Sciences; ArgentinaFil: Golpich, Mojtaba. University Kebangsaan Malaysia Medical Centre; MalasiaFil: Nawrotek, Katarzyna. University Of Lodz; ArgentinaFil: Paid, Ramesh K.. Indian Institute of Chemical Biology; IndiaFil: Shahidzadeh, Sheila M.. Syracuse University; Estados UnidosFil: Piermartiri, Tetsade. Universidade Federal de Santa Catarina; BrasilFil: Amini, Elham. University Kebangsaan Malaysia Medical Centre; MalasiaFil: Pastor, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia ; ArgentinaFil: Wilson, Yvette. University of Melbourne; AustraliaFil: Adeniyi, Philip A.. Afe Babalola University; NigeriaFil: Datusalia, Ashok K.. National Brain Research Centre; IndiaFil: Vafadari, Benham. Polish Academy of Sciences; ArgentinaFil: Saini, Vedangana. University of Nebraska; Estados UnidosFil: Suárez Pozos, Edna. Instituto Politécnico Nacional; MéxicoFil: Kushwah, Neetu. Defence Institute of Physiology and Allied Sciences; IndiaFil: Fontanet, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia ; ArgentinaFil: Turner, Anthony J.. University of Leeds; Reino Unid

Multimodal Strategies of Host-Seeking Mosquitoes

Mosquitoes use multiple sensory modalities, including olfaction, thermosensation, and vision, to hunt human hosts and obtain a blood-meal for egg production. Any individual sensory cue is an incomplete signal of a human host, and so a mosquito must integrate multimodal sensory information before committing to approaching and biting a person. Mosquito host-seeking behavior is thus a particularly fruitful model for studying multimodal integration because of its robustness, intricacy, and public health importance. Using tethered and free flight assays, we have teased apart responses to attractive visual and thermal cues in female Aedes aegypti, the yellow fever mosquito, uncovering their contributions to host-seeking decisions and distinctions in how they modulate their responses to those cues depending on CO₂, the most salient cue in human breath. We show that mosquitoes orient towards visual contrast in flight, regardless of CO₂ concentration, and then sense CO₂ to unlock thermotaxis towards potential hosts. Mosquitoes across their evolutionary lineage display an impressive variety of host choices, from mammals to cold-blooded frogs to leeches and earthworms, and the algorithms they use to weigh sensory host cues likely vary just as much. Our results illustrate how such weighting is performed in one species, providing a first glimpse into how general and contingent cues are integrated to produce host-seeking behavior in mosquitoes. With the rapid development of genetic and neuroscience tools in mosquitoes, we are poised to uncover the neuronal mechanisms underlying multimodal integration in these charismatic and deadly insects

Neural Representations of Courtship Song in the Drosophila Brain

Acoustic communication in drosophilid flies is based on the production and perception of courtship songs, which facilitate mating. Despite decades of research on courtship songs and behavior in Drosophila, central auditory responses have remained uncharacterized. In this study, we report on intracellular recordings from central neurons that innervate the Drosophila antennal mechanosensory and motor center (AMMC), the first relay for auditory information in the fly brain. These neurons produce graded-potential (nonspiking) responses to sound; we compare recordings from AMMC neurons to extracellular recordings of the receptor neuron population [Johnston's organ neurons (JONs)]. We discover that, while steady-state response profiles for tonal and broadband stimuli are significantly transformed between the JON population in the antenna and AMMC neurons in the brain, transient responses to pulses present in natural stimuli (courtship song) are not. For pulse stimuli in particular, AMMC neurons simply low-pass filter the receptor population response, thus preserving low-frequency temporal features (such as the spacing of song pulses) for analysis by postsynaptic neurons. We also compare responses in two closely related Drosophila species, Drosophila melanogaster and Drosophila simulans, and find that pulse song responses are largely similar, despite differences in the spectral content of their songs. Our recordings inform how downstream circuits may read out behaviorally relevant information from central neurons in the AMMC

Representations of Reward and Movement in Drosophila Dopaminergic Neurons

The neuromodulator dopamine is known to influence both immediate and future behavior, motivating and invigorating an animal’s ongoing movement but also serving as a reinforcement signal to instruct learning. Yet it remains unclear whether this dual role of dopamine involves the same dopaminergic pathways. Although reward-responsive dopaminergic neurons display movement-related activity, debate continues as to what features of an individual’s experience these motor-correlates correspond and how they influence concurrent behavior. The mushroom body, a prominent neuropil in the brain of the fruit fly Drosophila melanogaster, is richly innervated by dopaminergic neurons that play an essential role in the formation of olfactory associations. While dopaminergic neurons respond to reward and punishment to drive associative learning, they have also been implicated in a number of adaptive behaviors and their activity correlates with the behavioral state of an animal and its coarse motor actions. Here, we take advantage of the concise circuit architecture of the Drosophila mushroom body to investigate the nature of motor-related signals in dopaminergic neurons that drive associative learning. In vivo functional imaging during naturalistic tethered locomotion reveals that the activity of different subsets of mushroom body dopaminergic neurons reflects distinct aspects of movement. To gain insight into what facets of an animal’s experience are represented by these movement-related signals, we employed a closed loop virtual reality paradigm to monitor neural activity as animals track an olfactory stimulus and are actively engaged in a goal-directed and sensory-motivated behavior. We discover that odor responses in dopaminergic neurons correlate with the extent to which an animal tracks upwind towards the fictive odor source. In different experimental contexts where distinct motor actions were required to track the odor, dopaminergic neurons become emergently linked to the behavioral metric most relevant for effective olfactory navigation. Subsets of dopaminergic neurons were correlated with the strength of upwind tracking regardless of the identity of the odor and remained so even after the satiety state of an animal was altered. We proceed to demonstrate that transient inhibition of dopaminergic neurons that are positively correlated with upwind tracking significantly diminishes the normal approach responses to an appetitive olfactory cue. Accordingly, activation of those same dopaminergic neurons enhances approach to an odor and even drives upwind tracking in clean air alone. Together, these results reveal that the same dopaminergic pathways that convey reinforcements to instruct learning also carry representations of an animal’s moment-by-moment movements and actively influence behavior. The complex activity patterns of mushroom body dopaminergic neurons therefore represent neither purely sensory nor motor variables but rather reflect the goal or motivation underlying an animal’s movements. Our data suggest a fundamental coupling between reinforcement signals and motivation-related locomotor representations within dopaminergic circuitry, drawing a striking parallel between the mushroom body dopaminergic neurons described here and the emerging understanding of mammalian dopaminergic pathways. The apparent conservation in dopaminergic neuromodulatory networks between mammals and insects suggests a shared logic for how neural circuits assign meaning to both sensory stimuli and motor actions to generate flexible and adaptive behavior

Characterization of mating behaviour of the female fruit fly using machine vision

Courtship behaviour is the means for the animals to select their partner for reproduction. The fruit fly, Drosophila melanogaster, exhibit a complex courtship behaviour. Nearly all studies of D. melanogaster courtship have focused exclusively on the male behaviour. Female pre-copulatory behaviour is often relegated to ‘accepting’ or ‘rejecting’ of mating, and how females interact with males remains largely unknown. The aim of this study is to quantify and describe the mating behaviour of the female D. melanogaster. D. melanogaster is a model system that offers many genetic tools and when coupled with the recent technologies for neuronal manipulation, mapping and behavioural characterization, it has the potential to reveal the neurons involved in a particular behaviour. We analyzed the behaviour of the wild-type (WT) female fly by collecting information of the flies’ position during courtship using a tracking system and by automatically detecting specific behaviours using an automatic classifier. We found that WT flies displayed courtship acts and mating responses differently depending on their geographical origin strains. The automatic classes were developed in a machine learning system, to allow a faster and reliable behavioural analysis. In future work, the automatic classes developed in this research will be key to continue the female behaviour characterization

Coordinating morphology with behavior during development: an integrative approach from a fly perspective

Animals in the wild live in highly variable and unpredictable environments. This variation in their habitat induces animals, at all stages of their development, to make decisions about what to eat, where to live, and with whom to associate. Additionally, animals like insects show dramatic restructuring of their morphology across life stages, which is accompanied by alterations in their behavior to match stage-specific functions. Finally, in a process called developmental plasticity, environmental conditions feed back onto developmental mechanisms producing animals with stage-specific variation in both morphological and behavioral traits. In this review, we use examples from insects to explore the idea that animals are integrated units where stage-specific morphological and neurological traits develop together to increase individual fitness within their natural environments. We hypothesize that the same mechanisms act to alter both morphological and behavioral traits in response to the environment in which an organism develops. For example, in insects the steroid hormone ecdysone orchestrates the restructuring of the body from larva to adult form during metamorphosis at the same time as it rebuilds the central nervous system. The remodeling of both body form and nervous system structure results in behavioral alterations that match the morphological functions of the emerging adult. We review relevant findings from the fruit fly Drosophila melanogaster, combining insights from different fields like developmental biology, neurobiology and developmental plasticity. Finally, we highlight how insights drawn from D. melanogaster can be used as a model in future efforts to understand how developmental processes modify behavioral responses to environmental change in a stage-specific manner in other animals.info:eu-repo/semantics/publishedVersio

Novel circuits involved in Drosophila melanogaster virgin female sexual behaviours

"Courtship is a set of species-specific behaviours that provide a way by which male and female communicate, allowing the display of fitness of one sex (male) to the other (female) and leading to mating. This innate behaviour present in all animals, is crucial for reproduction and species survival. In Drosophila melanogaster, courtship consists of a series of stereotyped actions performed by the male towards the female, while she evaluates him by the sensory cues presented to her. At the end, the male may decide to attempt copulation, but it is the female who will decide whether or not to mate. (...)

Tracking nutrient decisions in Drosophila melanogaster

Animals integrate external sensory information and current metabolic needs to adapt their behavior in order to survive. Accordingly, many organisms can detect an internal nutritional imbalance and adjust their nutritional choices to restore homeostasis. Detailed quantitative analyses of nutrient-choice behaviors are needed to deepen our understanding of how neural circuits integrate internal state information and drive compensatory behavior when facing metabolic challenges. During this project, we developed an automated video tracking setup to characterize how metabolic and reproductive states interact to shape exploitation and exploration decisions taken by the adult fruit fly Drosophila melanogaster, to achieve nutritional homeostasis. We find that these two states have specific effects on the decisions to stop on and leave proteinaceous food patches. Furthermore, the internal nutrient state defines the exploration-exploitation trade-off: nutrient deprived flies focus on specific patches while satiated flies explore more globally. We provide few examples of how our paradigm could be used in the dissection of the genetic and neuronal pathways underlying nutrient decisions: First, we show that olfaction is not required for the compensatory high yeast feeding after amino acid deprivation, but that it mediates the efficient recognition of yeast as an appropriate food source in mated females. Second, we show that octopamine is required to mediate homeostatic postmating responses without affecting internal nutrient sensing. Third, we show how gustation is required to sustain interest for protein-rich resources upon amino acid deprivation. Our results provide a quantitative description of how the fly changes behavioral decisions to achieve homeostatic nutrient balancing and provide a framework for future detailed mechanistic dissection of such decisions