Dopamine release at the time of a predicted aversive outcome causally controls the trajectory and expression of conditioned behavior.

Dopamine release in the nucleus accumbens (NAc) is causally linked to adaptive aversive learning, and its dysregulation is a core phenotype in anxiety and stress disorders. Here, we record NAc core dopamine during a task where mice learn to discriminate between cues signaling two types of outcomes: (1) footshock presentation and (2) footshock omission. We show that dopamine release is evoked by footshock omission. This dopamine response is largest when the omission is unexpected and decreases over learning, and artificially increasing this signal disrupts discrimination learning. Conversely, optogenetic inhibition of dopamine responses to the footshock itself impairs learning. Finally, theory-driven computational modeling suggests that these effects can be explained by dopamine signaling the perceived saliency of predicted aversive events. Together, we elucidate the role of NAc dopamine in aversive learning and offer potential avenues for understanding the neural mechanisms involved in anxiety and stress disorders.

Monitoring Fast Synaptic Transmission of Neuromodulatory Transmitters To Define Drug Effects in the Brain.

Catecholaminergic systems are involved in a range of psychiatric disorders and are central mediators of the effects of stimulants on the brain and behavior. Advances in analytical detection methods paired with creative application of these approaches allow for recording noradrenergic and dopaminergic systems in the brain in isolation with subsecond resolution. Pauly et al. ( ACS Chem. Neurosci. 2023, 10.1021/acschemneuro.2c00689) define the distinct and differential mechanisms of methamphetamine enantiomers on dopamine and norepinephrine release, giving critical insights into the pharmacodynamic properties of a stimulant that is both abused and used clinically.

Taste-Odor Association Learning Alters the Dynamics of Intraoral Odor Responses in the Posterior Piriform Cortex of Awake Rats.

How an odor is perceived is to a large extent dependent on the context in which that odor is (or has been) experienced. For example, experiencing an odor in mixture with taste during consumption can instill taste qualities in the percept of that odor (e.g., vanilla, an odor, has a gustatory quality: sweet). How associative features of odors are encoded in the brain remains unknown, but previous work suggests an important role for ongoing interactions between piriform cortex and extraolfactory systems. Here, we tested the hypothesis that piriform cortex dynamically encodes taste associations of odors. Rats were trained to associate one of two odors with saccharin; the other odor remained neutral. Before and after training, we tested preferences for the saccharin-associated odor versus the neutral odor, and recorded spiking responses from ensembles of neurons in posterior piriform cortex (pPC) to intraoral delivery of small drops of the same odor solutions. The results show that animals successfully learned taste-odor associations. At the neural level, single pPC neuron responses to the saccharin-paired odor were selectively altered following conditioning. Altered response patterns appeared after 1 s following stimulus delivery, and successfully discriminated between the two odors. However, firing rate patterns in the late epoch appeared different from firing rates early in the early epoch (<1 s following stimulus delivery). That is, in different response epoch, neurons used different codes to represent the difference between the two odors. The same dynamic coding scheme was observed at the ensemble level.

Multisensory integration of orally-sourced gustatory and olfactory inputs to the posterior piriform cortex in awake rats.

Flavour refers to the sensory experience of food, which is a combination of sensory inputs sourced from multiple modalities during consumption, including taste and odour. Previous work has demonstrated that orally-sourced taste and odour cues interact to determine perceptual judgements of flavour stimuli, although the underlying cellular- and circuit-level neural mechanisms remain unknown. We recently identified a region of the piriform olfactory cortex in rats that responds to both taste and odour stimuli. Here, we investigated how converging taste and odour inputs to this area interact to affect single neuron responsiveness ensemble coding of flavour identity. To accomplish this, we recorded spiking activity from ensembles of single neurons in the posterior piriform cortex (pPC) in awake, tasting rats while delivering taste solutions, odour solutions and taste + odour mixtures directly into the oral cavity. Our results show that taste and odour inputs evoke highly selective, temporally-overlapping responses in multisensory pPC neurons. Comparing responses to mixtures and their unisensory components revealed that taste and odour inputs interact in a non-linear manner to produce unique response patterns. Taste input enhances trial-by-trial decoding of odour identity from small ensembles of simultaneously recorded neurons. Together, these results demonstrate that taste and odour inputs to pPC interact in complex, non-linear ways to form amodal flavour representations that enhance identity coding. KEY POINTS: Experience of food involves taste and smell, although how information from these different senses is combined by the brain to create our sense of flavour remains unknown. We recorded from small groups of neurons in the olfactory cortex of awake rats while they consumed taste solutions, odour solutions and taste + odour mixtures. Taste and smell solutions evoke highly selective responses. When presented in a mixture, taste and smell inputs interacted to alter responses, resulting in activation of unique sets of neurons that could not be predicted by the component responses. Synergistic interactions increase discriminability of odour representations. The olfactory cortex uses taste and smell to create new information representing multisensory flavour identity.

The influence of reinforcement schedule on experience-dependent changes in motivation.

The progressive ratio procedure is used across fields to assess motivation for different reinforcers, define the effects of experimental interventions on motivation, and determine experience-dependent changes in motivation. However, less is known about how operant training schedules affect performance on this widely utilized task. Here we designed an experiment to examine the effect of variable ratio versus fixed ratio training schedules of reinforcement on progressive ratio performance while holding other performance variables constant between groups. We found a robust increase in maximum ratio completed between the pretest and posttraining test highlighting a robust training effect on progressive ratio performance. However, it did not matter if the training was under a fixed or variable ratio schedule. Additionally, we show that neither individual rates during training nor extinction responding correlated with maximum ratio achieved during the sessions. Finally, we show that rates during the training sessions do correlate with extinction performance, suggesting that these variables measure a different aspect of performance that does not predict motivation.

Odor mixture perception during flavor consumption in rats.

Odor mixtures can be perceived as configural (i.e., different from their components) or elemental (i.e., similar to their components). Previous work demonstrates that these perceptual modes are determined by both peripheral and central interactions among mixture components. Flavor consumption is associated with unique peripheral and central odor processing mechanisms, but how this context affects perception of odor mixtures remains unknown. Here, we used a flavor consumption task in rats to measure preferences for solutions of binary odor mixtures and their components. In contrast to previous findings using identical mixtures in other contexts, our results demonstrate that rats employ elemental mixture processing strategies in the context of consumption. We discuss potential peripheral and central mechanisms that could explain unique mixture perception during consumption. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Elastic energy storage across speeds during steady-state hopping of desert kangaroo rats (Dipodomys deserti).

Small bipedal hoppers, including kangaroo rats, are not thought to benefit from substantial elastic energy storage and return during hopping. However, recent species-specific material properties research suggests that, despite relative thickness, the ankle extensor tendons of these small hoppers are considerably more compliant than had been assumed. With faster locomotor speeds demanding higher forces, a lower tendon stiffness suggests greater tendon deformation and thus a greater potential for elastic energy storage and return with increasing speed. Using the elastic modulus values specific to kangaroo rat tendons, we sought to determine how much elastic energy is stored and returned during hopping across a range of speeds. In vivo techniques were used to record tendon force in the ankle extensors during steady-speed hopping. Our data support the hypothesis that the ankle extensor tendons of kangaroo rats store and return elastic energy in relation to hopping speed, storing more at faster speeds. Despite storing comparatively less elastic energy than larger hoppers, this relationship between speed and energy storage offers novel evidence of a functionally similar energy storage mechanism, operating irrespective of body size or tendon thickness, across the distal muscle-tendon units of both small and large bipedal hoppers.

Stimulation of mu opioid, but not GABAergic, receptors of the lateral habenula alters free feeding in rats.

Overconsumption, or eating beyond the point of homeostasis, is a key feature in the development of obesity. Although people are consuming beyond the point of homeostasis, they are not consuming constantly or indefinitely. Thus, there is likely a mechanism that acts to terminate periods of food intake at some point beyond satiation and prior to aversion, or the negative effects of extreme excess (nausea, bloating, etc.). The purpose of the present study was to assess the lateral habenula as a candidate region for such a mechanism, due to its connectivity to midbrain reward circuitry, sensitivity to metabolic signaling, and pronounced role in drug-related motivated behaviors. Two groups of male Sprague-Dawley rats were surgically implanted with bilateral guide cannula targeting the LHb. Rats were then habituated to feeding chambers, wherein locomotion and food intake were monitored throughout a two-hour session. One experimental group was tested in the presence of rat chow; the second group was instead given access to a sweetened fat diet. Each subject separately received a 0.2 µL vehicle (0.9% saline solution) and baclofen-muscimol (50 ng/0.2 µL of each drug dissolved in 0.9% saline) injection. Additionally, on a third injection day, each rat received an injection of mu-opioid agonist DAMGO (0.1 µg/0.2 µL) prior to placement in the chamber. LHb inactivation did not result in significant alterations in feeding behavior, but produced a consistent increase in locomotor activity in both experimental groups. Mu-opioid receptor stimulation increased feeding on standard chow, but decreased intake of the sweetened-fat diet. Although LHb inactivation did not increase feeding as predicted, the novel finding that mu opioid receptor stimulation decreased feeding on a highly palatable diet, but increased intake of rat chow, highlights a differential role for the LHb in regulating hedonic consummatory behavior.

Comparing dopamine release, uptake, and D2 autoreceptor function across the ventromedial to dorsolateral striatum in adolescent and adult male and female rats.

Adolescence is characterized by changes in behavior, such as increases in sensation seeking and risk taking, and increased vulnerability to developing a range of psychiatric disorders, including substance abuse disorders (SUD) and mood disorders. The mesolimbic dopamine system plays an essential role in mediating these behaviors and disorders. Therefore, it is imperative to understand how the dopamine system and its regulation are changing during this period of development. Here, we used ex vivo fast scan cyclic voltammetry to compare stimulated dopamine release and its local circuitry regulation between early adolescent and adult male and female Sprague-Dawley rats. We found that, compared to adults, adolescent males have decreased stimulated dopamine release in the NAc core, while adolescent females have increased dopamine release in the NAc shell, NAc core, and DMS. We also found sex- and region-specific differences in other dopamine dynamics, including maximal dopamine uptake (Vmax), release across a range of stimulation frequencies, and autoreceptor regulation of dopamine release. Better understanding how the dopamine system develops during adolescence will be imperative for understanding what mediates adolescent vulnerability to developing psychiatric disorders and how disruptions during this period of reorganization could alter behaviors and vulnerability into adulthood.