The sunk cost effect refers to the fact that human decisions are consistently influenced by previous irrecoverable and irrelevant costs. Recent neuroimaging experiments suggest that the dorsolateral prefrontal cortex (dlPFC) plays a pivotal role in the sunk cost effect yet the causal and neurocomputational role of the dlPFC remains elusive. In this study, two cohorts of healthy human male and female adults were recruited to complete a novel two-step decision-making task during the anodal-sham or cathodal-sham high-definition transcranial direct current stimulation (HD-tDCS) over the dlPFC, respectively. Consistent with previous studies, we showed that the sunk cost deterred participants from making further investment and therefore engendered a de-escalation effect. Such behavior can be captured by a weighted mental accounting model with a recalibrated reference point in which the direction and magnitude of the sunk cost effects hinge on the decision weights apportioned to the option values. Interestingly, ...

Aggressive behavior is one of the most conserved social interactions in nature and serves as a crucial evolutionary trait. Serotonin (5-HT) plays a key role in the regulation of our emotions such as anxiety and aggression, but which molecules and mechanisms in the serotonergic system are involved in violent behavior is still unknown. In this study we show that deletion of the P/Q-type calcium channel selectively from serotonergic neurons in the dorsal raphe nuclei (DRN) augments aggressive behavior in male mice, while anxiety is not affected. These mice demonstrated increased induction of the immediate early gene c-fos and in vivo serotonergic firing activity in the DRN. The ventrolateral part of the ventromedial hypothalamus (VHMvl) is also a prominent region of the brain mediating aggression. We confirmed a monosynaptic projection from the DRN to the VHMvl and silencing these projections with an inhibitory designer receptor exclusively activated by a designer drug (DREADD) effectively reduced aggressive ...

Visual neural plasticity and V1 saliency-detection are vital for efficient-coding of dynamically changing visual inputs. However, how does neural plasticity contribute to saliency-detection of temporal-statistically distributed visual stream remains unclear. Therefore, we adopted randomly presented but unevenly distributed stimuli with multiple orientations, and examined the single-unit responses evoked by this biased orientation-adaptation protocol, by single-unit recordings in the visual thalamo-ventral pathway of cats (of either sex). We found neuronal responses potentiated when the probability of biased orientation was slightly higher than other non-biased ones, and suppressed when the probability became much higher. This single-neuronal short-term bidirectional-plasticity is selectively induced by optimal stimuli, but inter-ocularly transferable. It is inducible in LGN, Area 17 and Area 21a with distinct and hierarchically progressive patterns. With the results of latency-analysis, receptive-field str...

Mounting evidence suggests distinct functional contributions of the anterior and posterior hippocampus to autobiographical memory retrieval, but how these subregions function under different retrieval demands as memories age is not yet understood. Specifically, autobiographical memory retrieval is not a homogeneous process; rather, it is thought to consist of the following multiple stages: an early stage of memory construction and a later stage of detailed elaboration, which may differently engage the hippocampus over time. In the present study, we analyzed data from 40 participants (23 female/17 male) who constructed and overtly elaborated on recent and remote memories in response to picture cues in the fMRI scanner. We previously reported a temporal gradient in the posterior hippocampus during the elaboration period of autobiographical retrieval, with posterior hippocampal activation observed for recent but not remote time points. Here, we consider the previously unanalyzed construction stage of retrieva...

Opioid misuse among pregnant women is rapidly increasing in the United States. The number of maternal opioid-related diagnoses increased by 131% in the last ten years, resulting in an increased number of infants exposed to opioids in utero and a subsequent increase in infants developing neonatal abstinence syndrome (NAS). The most prescribed treatment to combat maternal opioid use disorder is buprenorphine, a partial μ-opioid receptor agonist and κ-opioid receptor antagonist. Buprenorphine treatment effectively reduces NAS but has been associated with disrupted cortical development and neurodevelopmental consequences in childhood. Less is known about the long-term neurodevelopmental consequences following buprenorphine exposure in utero . Previous research has shown that gestational buprenorphine exposure can induce anxiety- and depressive-like phenotypes in adult rats, suggesting that exposure to buprenorphine in utero may render individuals more susceptible to psychiatric illness in adulthood. A common p...

Drinking behavior has been used in basic research to study metabolism, motivation, decision-making and different aspects of health problems, such as anhedonia and alcohol use disorders. In the majority of studies, liquid intake is measured by weighing the bottles before and after the experiment. This method does not tell much about the drinking microstructure, e.g., licking bouts and periods of preference for each liquid, which could be valuable to understand drinking behavior. To improve the data acquisition of drinking microstructure, companies have developed lick-o-meters devices that acquire timestamps when animals approach or drink from a specific sipper. Nevertheless, commercially available devices have elevated costs. Here, we present a low-cost alternative for a lick-o-meter system that allows wireless data acquisition of licking from eight cages with two sippers each. We run a three-phase validation protocol to ensure 1) proper choice of the sensor to detect licks; 2) adaptation of the device to a...

CRISPR/Cas9-mediated knock-in methods enable the labeling of individual endogenous proteins to faithfully determine their spatiotemporal distribution in cells. However, reliable multiplexing of knock-in events in neurons remains challenging because of cross talk between editing events. To overcome this, we developed conditional activation of knock-in expression (CAKE), allowing efficient, flexible, and accurate multiplex genome editing in rat neurons. To diminish cross talk, CAKE is based on sequential, recombinase-driven guide RNA (gRNA) expression to control the timing of genomic integration of each donor sequence. We show that CAKE is broadly applicable to co-label various endogenous proteins, including cytoskeletal proteins, synaptic scaffolds, ion channels and neurotransmitter receptor subunits. To take full advantage of CAKE, we resolved the nanoscale co-distribution of endogenous synaptic proteins using super-resolution microscopy, demonstrating that their co-organization depends on synapse size. Fi...

In similar states, neural circuits produce similar outputs across individuals despite substantial interindividual variability in neuronal ionic conductances and synapses. Circuit states are largely shaped by neuromodulators that tune ionic conductances. It is therefore possible that, in addition to producing flexible circuit output, neuromodulators also contribute to output similarity despite varying ion channel expression. We studied whether neuromodulation at saturating concentrations can increase the output similarity of a single identified neuron across individual animals. Using the LP neuron of the crab stomatogastric ganglion (STG), we compared the variability of f-I curves and rebound properties in the presence of neuropeptides. The two neuropeptides we used converge to activate the same target current, which increases neuronal excitability. Output variability was lower in the presence of the neuropeptides, regardless of whether the neuropeptides significantly changed the mean of the corresponding p...

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that results in intellectual disability and, in ∼50% of patients, autism spectrum disorder. The protein products that are altered in TSC (TSC1 and TSC2) form a complex to inhibit the mammalian target of rapamycin [mTOR; mTOR complex 1 (mTORC1)] pathway. This pathway has been shown to affect the process of mRNA translation through its action on ribosomal protein S6 and 4-elongation binding protein 1. It is thought that mutations in the TSC proteins lead to upregulation of the mTORC1 pathway and consequently an increase in protein synthesis. Unexpectedly, our previous study of a mouse model of TSC ( Tsc2Djk +/) demonstrated decreased in vivo rates of protein synthesis throughout the brain. In the present study, we confirm those results in another Tsc2 +/− mouse model, one with a different mutation locus and on a mixed background ( Tsc2Mjg +/−). We also examine mTORC1 signaling and possible effects of prior isoflurane anesthesia. Because measu...

The nucleus accumbens shell (NAcSh) is a key brain region where environmental cues acquire incentive salience to reinforce motivated behaviors. Principal medium spiny neurons (MSNs) in the NAcSh receive extensive glutamatergic projections from limbic regions, among which, the ventral hippocampus (vH) transmits information enriched in contextual cues, and the basolateral amygdala (BLA) encodes real-time arousing states. The vH and BLA project convergently to NAcSh MSNs, both activated in a time-locked manner upon a cue-conditioned motivational action. In brain slices prepared from male and female mice, we show that co-activation of the two projections induces long-term potentiation (LTP) at vH-to-NAcSh synapses without affecting BLA-to-NAcSh synapses, revealing a heterosynaptic mechanism through which BLA signals persistently increase the temporally contingent vH-to-NAcSh transmission. Furthermore, this LTP is more prominent in dopamine D1 receptor-expressing (D1) MSNs than D2 MSNs and can be prevented by i...