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

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.

Activation of adenosine A2A receptors in the olfactory tubercle promotes sleep in rodents.

The olfactory tubercle (OT), an important nucleus in processing sensory information, has been reported to change cortical activity under odor. However, little is known about the physiological role and mechanism of the OT in sleep-wake regulation. The OT expresses abundant adenosine A2A receptors (A2ARs), which are important in sleep regulation. Therefore, we hypothesized that the OT regulates sleep via A2ARs. This study examined sleep-wake profiles through electroencephalography and electromyography recordings with pharmacological and chemogenetic manipulations in freely moving rodents. Compared with their controls, activation of OT A2ARs pharmacologically and OT A2AR neurons via chemogenetics increased non-rapid eye movement sleep for 5 and 3 h, respectively, while blockade of A2ARs decreased non-rapid eye movement sleep. Tracing and electrophysiological studies showed OT A2AR neurons projected to the ventral pallidum and lateral hypothalamus, forming inhibitory innervations. Together, these findings indicate that A2ARs in the OT play an important role in sleep regulation.

Glutamatergic Neurons in the Piriform Cortex Influence the Activity of D1- and D2-Type Receptor-Expressing Olfactory Tubercle Neurons.

Sensory cortices process stimuli in manners essential for perception. Very little is known regarding interactions between olfactory cortices. The piriform "primary" olfactory cortex, especially its anterior division (aPCX), extends dense association fibers into the ventral striatum's olfactory tubercle (OT), yet whether this corticostriatal pathway is capable of shaping OT activity, including odor-evoked activity, is unknown. Further unresolved is the synaptic circuitry and the spatial localization of OT-innervating PCX neurons. Here we build upon standing literature to provide some answers to these questions through studies in mice of both sexes. First, we recorded the activity of OT neurons in awake mice while optically stimulating principal neurons in the aPCX and/or their association fibers in the OT while the mice were delivered odors. This uncovered evidence that PCX input indeed influences OT unit activity. We then used patch-clamp recordings and viral tracing to determine the connectivity of aPCX neurons upon OT neurons expressing dopamine receptor types D1 or D2, two prominent cell populations in the OT. These investigations uncovered that both populations of neurons receive monosynaptic inputs from aPCX glutamatergic neurons. Interestingly, this input originates largely from the ventrocaudal aPCX. These results shed light on some of the basic physiological properties of this pathway and the cell-types involved and provide a foundation for future studies to identify, among other things, whether this pathway has implications for perception.SIGNIFICANCE STATEMENT Sensory cortices interact to process stimuli in manners considered essential for perception. Very little is known regarding interactions between olfactory cortices. The present study sheds light on some of the basic physiological properties of a particular intercortical pathway in the olfactory system and provides a foundation for future studies to identify, among other things, whether this pathway has implications for perception.

Effects of Oxytocin on the Levels and Metabolism of Monoamines in the Brain of White Outbred Mice during Long-Term Social Isolation.

The effects of intranasal administration of oxytocin on the levels and metabolism of monoamines in symmetrical structures of the brain of white outbred mice kept under conditions of long-term social isolation were studied by HPLC. Disappearance of initial right-sided asymmetry in the content of dopamine metabolites in the striatum, increased 5-hydroxyacetic acid content in the right striatum, and disappearance of the initial left-sided asymmetry in serotonin level in the cortex were noted; we also found a decrease in norepinephrine content in the left hippocampus with appearance of asymmetry and higher content in the right olfactory tubercle. It can be hypothesized that minor changes in the serotoninergic and dopaminergic systems against the background of high reactivity of noradrenergic system represent specific response of the brain to oxytocin in aggressive animals.

Odor- and state-dependent olfactory tubercle local field potential dynamics in awake rats.

The olfactory tubercle (OT), a trilaminar structure located in the basal forebrain of mammals, is thought to play an important role in olfaction. While evidence has accumulated regarding the contributions of the OT to odor information processing, studies exploring the role of the OT in olfaction in awake animals remain unavailable. In the present study, we begin to address this void through multiday recordings of local field potential (LFP) activity within the OT of awake, freely exploring Long-Evans rats. We observed spontaneous OT LFP activity consisting of theta- (2-12 Hz), beta- (15-35 Hz) and gamma- (40-80 Hz) band activity, characteristic of previous reports of LFPs in other principle olfactory structures. Beta- and gamma-band powers were enhanced upon odor presentation. Simultaneous recordings of OT and upstream olfactory bulb (OB) LFPs revealed odor-evoked LFP power at statistically similar levels in both structures. Strong spectral coherence was observed between the OT and OB during both spontaneous and odor-evoked states. Furthermore, the OB theta rhythm more strongly cohered with the respiratory rhythm, and respiratory-coupled theta cycles in the OT occurred following theta cycles in the OB. Finally, we found that the animal's internal state modulated LFP activity in the OT. Together, these data provide initial insights into the network activity of the OT in the awake rat, including spontaneous rhythmicity, odor-evoked modulation, connectivity with upstream sensory input, and state-dependent modulation.