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1. A high-throughput method to deliver targeted optogenetic stimulation to moving C. elegans populations

   https://doi.org/10.1371/journal.pbio.3001524  

   Liu, Mochi; Kumar, Sandeep; Sharma, Anuj K.; Leifer, Andrew M. (January 2022, PLOS Biology)

   Sengupta, Piali (Ed.)

   We present a high-throughput optogenetic illumination system capable of simultaneous closed-loop light delivery to specified targets in populations of moving Caenorhabditis elegans . The instrument addresses three technical challenges: It delivers targeted illumination to specified regions of the animal’s body such as its head or tail; it automatically delivers stimuli triggered upon the animal’s behavior; and it achieves high throughput by targeting many animals simultaneously. The instrument was used to optogenetically probe the animal’s behavioral response to competing mechanosensory stimuli in the the anterior and posterior gentle touch receptor neurons. Responses to more than 43,418 stimulus events from a range of anterior–posterior intensity combinations were measured. The animal’s probability of sprinting forward in response to a mechanosensory stimulus depended on both the anterior and posterior stimulation intensity, while the probability of reversing depended primarily on the anterior stimulation intensity. We also probed the animal’s response to mechanosensory stimulation during the onset of turning, a relatively rare behavioral event, by delivering stimuli automatically when the animal began to turn. Using this closed-loop approach, over 9,700 stimulus events were delivered during turning onset at a rate of 9.2 events per worm hour, a greater than 25-fold increase in throughput compared to previous investigations. These measurements validate with greater statistical power previous findings that turning acts to gate mechanosensory evoked reversals. Compared to previous approaches, the current system offers targeted optogenetic stimulation to specific body regions or behaviors with many fold increases in throughput to better constrain quantitative models of sensorimotor processing. 

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2. Phasic dopamine reinforces distinct striatal stimulus encoding in the olfactory tubercle driving dopaminergic reward prediction

   https://doi.org/10.1038/s41467-020-17257-7  

   Oettl, Lars-Lennart; Scheller, Max; Filosa, Carla; Wieland, Sebastian; Haag, Franziska; Loeb, Cathrin; Durstewitz, Daniel; Shusterman, Roman; Russo, Eleonora; Kelsch, Wolfgang (December 2020, Nature Communications)

   Abstract The learning of stimulus-outcome associations allows for predictions about the environment. Ventral striatum and dopaminergic midbrain neurons form a larger network for generating reward prediction signals from sensory cues. Yet, the network plasticity mechanisms to generate predictive signals in these distributed circuits have not been entirely clarified. Also, direct evidence of the underlying interregional assembly formation and information transfer is still missing. Here we show that phasic dopamine is sufficient to reinforce the distinctness of stimulus representations in the ventral striatum even in the absence of reward. Upon such reinforcement, striatal stimulus encoding gives rise to interregional assemblies that drive dopaminergic neurons during stimulus-outcome learning. These assemblies dynamically encode the predicted reward value of conditioned stimuli. Together, our data reveal that ventral striatal and midbrain reward networks form a reinforcing loop to generate reward prediction coding. 

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3. Pavlovian occasion setting in human fear and appetitive conditioning: Effects of trait anxiety and trait depression

   https://doi.org/10.1016/j.brat.2021.103986  

   Zbozinek, Tomislav D; Wise, Toby; Perez, Omar D; Qi, S; Fanselow, Michael S; Mobbs, Dean (December 2021, Behaviour research and therapy)

   Contexts and discrete stimuli often hierarchically influence the association between a stimulus and outcome. This phenomenon, called occasion setting, is central to modulation-based Pavlovian learning. We conducted two experiments with humans in fear and appetitive conditioning paradigms, training stimuli in differential conditioning, feature-positive discriminations, and feature-negative discriminations. We also investigated the effects of trait anxiety and trait depression on these forms of learning. Results from both experiments showed that participants were able to successfully learn which stimuli predicted the electric shock and monetary reward outcomes. Additionally, as hypothesized, the stimuli trained as occasion setters had little-to-no effect on simple reinforced or non-reinforced stimuli, suggesting the former were indeed occasion setters. Lastly, in fear conditioning, trait anxiety was associated with increases in fear of occasion setter/conditional stimulus compounds; in appetitive conditioning, trait depression was associated with lower expectations of monetary reward for the trained negative occasion setting compound and transfer of the negative occasion setter to the simple reinforced stimulus. These results suggest that clinically anxious individuals may have enhanced fear of occasion setting compounds, and clinically depressed individuals may expect less reward with compounds involving the negative occasion setter. 

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4. Sparse high-dimensional decomposition of non-primary auditory cortical receptive fields

   https://doi.org/10.1371/journal.pcbi.1012721  

   Mukherjee, Shoutik; Babadi, Behtash; Shamma, Shihab (January 2025, PLOS Computational Biology)

   Kumar, Arvind (Ed.)

   Characterizing neuronal responses to natural stimuli remains a central goal in sensory neuroscience. In auditory cortical neurons, the stimulus selectivity of elicited spiking activity is summarized by a spectrotemporal receptive field (STRF) that relates neuronal responses to the stimulus spectrogram. Though effective in characterizing primary auditory cortical responses, STRFs of non-primary auditory neurons can be quite intricate, reflecting their mixed selectivity. The complexity of non-primary STRFs hence impedes understanding how acoustic stimulus representations are transformed along the auditory pathway. Here, we focus on the relationship between ferret primary auditory cortex (A1) and a secondary region, dorsal posterior ectosylvian gyrus (PEG). We propose estimating receptive fields in PEG with respect to a well-established high-dimensional computational model of primary-cortical stimulus representations. These “cortical receptive fields” (CortRF) are estimated greedily to identify the salient primary-cortical features modulating spiking responses and in turn related to corresponding spectrotemporal features. Hence, they provide biologically plausible hierarchical decompositions of STRFs in PEG. Such CortRF analysis was applied to PEG neuronal responses to speech and temporally orthogonal ripple combination (TORC) stimuli and, for comparison, to A1 neuronal responses. CortRFs of PEG neurons captured their selectivity to more complex spectrotemporal features than A1 neurons; moreover, CortRF models were more predictive of PEG (but not A1) responses to speech. Our results thus suggest that secondary-cortical stimulus representations can be computed as sparse combinations of primary-cortical features that facilitate encoding natural stimuli. Thus, by adding the primary-cortical representation, we can account for PEG single-unit responses to natural sounds better than bypassing it and considering as input the auditory spectrogram. These results confirm with explicit details the presumed hierarchical organization of the auditory cortex. 

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5. Npas4a expression in the teleost forebrain is associated with stress coping style differences in fear learning

   https://doi.org/10.1038/s41598-021-91495-7  

   Baker, Matthew R.; Wong, Ryan Y. (December 2021, Scientific Reports)

   Abstract Learning to anticipate potentially dangerous contexts is an adaptive behavioral response to coping with stressors. An animal’s stress coping style (e.g. proactive–reactive axis) is known to influence how it encodes salient events. However, the neural and molecular mechanisms underlying these stress coping style differences in learning are unknown. Further, while a number of neuroplasticity-related genes have been associated with alternative stress coping styles, it is unclear if these genes may bias the development of conditioned behavioral responses to stressful stimuli, and if so, which brain regions are involved. Here, we trained adult zebrafish to associate a naturally aversive olfactory cue with a given context. Next, we investigated if expression of two neural plasticity and neurotransmission-related genes ( npas4a and gabbr1a ) were associated with the contextual fear conditioning differences between proactive and reactive stress coping styles. Reactive zebrafish developed a stronger conditioned fear response and showed significantly higher npas4a expression in the medial and lateral zones of the dorsal telencephalon (Dm, Dl), and the supracommissural nucleus of the ventral telencephalon (Vs). Our findings suggest that the expression of activity-dependent genes like npas4a may be differentially expressed across several interconnected forebrain regions in response to fearful stimuli and promote biases in fear learning among different stress coping styles. 

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