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Amin, F.

Publications and source records attributed to Amin, F..

3 recordsLinked to original sources

Avoidance engages dopaminergic punishment in Drosophila

It was classically suggested that behaviour can cause emotions (Darwin 1872). For example, smiling can make us feel happier, and in rodents the induced patterns of cardiac activity and breathing that are indicative of fear can in turn evoke it (Coles et al. 2022, Hsueh et al. 2023, Jhang et al. 2024). However, the adaptive significance of such feedback is unclear. We show that inducing backward movement, an element of avoidance behaviour in Drosophila, engages negative valence signals in these animals, and reveal the neuronal mechanisms and adaptive significance of this effect. We develop a paradigm with odours as conditioned stimuli paired with optogenetically induced backward movement instead of a punishing unconditioned stimulus, and combined these experiments with pharmacology, high-resolution video tracking, functional imaging, connectome analyses, and modelling. Our results show that backward movement engages dopaminergic punishment neurons and supports aversive memories. Such avoidance-to-punishment feedback counterbalances extinction learning and maintains learned avoidance, reducing the risk of further punishment. This can explain the long-standing "avoidance paradox", the observation that avoidance adaptively persists even when it is successful and no punishment is received (Bolles 1972). Our results provide a neurobiologically grounded argument for an integrated view of behaviour organization and valence processing.

neuroscience↗

Compromising tyrosine hydroxylase function establishes a delusion-like temporal profile of reinforcement by dopamine neurons in Drosophila

For a proper representation of the causal structure of the world, one must consider both evidence for and evidence against causality. To take punishment as an example, the causality of a stimulus is reasonable if the stimulus precedes punishment, whereas causality can be ruled out if the punishment occurred first. This is reflected in the associative principle of timing-dependent valence reversal: aversive memories are formed when a stimulus occurs before the punishment, whereas memories of appetitive valence are observed when a stimulus is presented upon its relieving termination. We map the temporal profile of punishment induced by optogenetic activation of the PPL1-01 neuron in the fly Drosophila melanogaster, and find that impairment of tyrosine hydroxylase function, either acutely by pharmacological methods or by cell-specific RNAi, i) enhances learning with a time gap between stimulus and PPL1-01 punishment (trace conditioning), ii) impairs learning when the stimulus immediately precedes PPL1-01 punishment (delay conditioning), and iii) prevents learning about a stimulus presented after PPL1-01 punishment has ceased (relief conditioning). This implies a delusion-like state in which causality is attributed to cues that do not merit it (better trace conditioning), whereas both credible evidence for and credible evidence against causality is not properly appreciated (worse delay and relief conditioning). Under conditions of low dopamine, we furthermore observe a compensatory role for serotonin that is pronounced in trace conditioning, weaker in delay conditioning, and absent in relief conditioning. We discuss a disturbed dopamine-serotonin balance as an endophenotype for the positive and cognitive symptoms in schizophrenia.

animal behavior and cognition↗

Associative learning in larval and adult Drosophila is impaired by the dopamine-synthesis inhibitor 3-Iodo-L-tyrosine

Across the animal kingdom, dopamine plays a crucial role in conferring reinforcement signals that teach animals about the causal structure of the world. In the fruit fly Drosophila melanogaster, the dopamine system has largely been studied using a rich genetic toolbox. Here, we suggest a complementary pharmacological approach applying the dopamine-synthesis inhibitor 3-Iodo-L-tyrosine (3IY), which causes acute systemic inhibition of dopamine signaling. Using Pavlovian conditioning, across developmental stages (3rd instar larva versus adult), valence domains (reward versus punishment), and types of reinforcement (natural versus optogenetically induced), we find that 3IY feeding specifically impairs associative learning, whereas additional feeding of L-3,4-dihydroxyphenylalanine (L-DOPA), a precursor of dopamine, rescues this impairment. This study establishes a simple, quick, and comparably low-cost approach that can be combined with the available genetic tools to manipulate and clarify the functions of the dopaminergic system - in D. melanogaster and other animals.

neuroscience↗