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 ...

Relapse is a major problem in treating methamphetamine use disorder. “Incubation of craving” during abstinence is a rat model for persistence of vulnerability to craving and relapse. While methamphetamine incubation has previously been demonstrated in male and female rats, it has not been demonstrated after withdrawal periods greater than 51 d and most mechanistic work used males. Here, we address both gaps. First, although methamphetamine intake was higher in males during self-administration training (6 h/d × 10 d), incubation was similar in males and females, with “incubated” craving persisting through withdrawal day (WD)100. Second, using whole-cell patch-clamp recordings in medium spiny neurons (MSNs) of the nucleus accumbens (NAc) core, we assessed synaptic levels of calcium-permeable AMPA receptors (CP-AMPARs), as their elevation is required for expression of incubation in males. In both sexes, compared with saline-self-administering controls, CP-AMPAR levels were significantly higher in methamphetam...

Women are twice as likely as men to experience emotional dysregulation after stress, resulting in substantially higher psychopathology for equivalent lifetime stress exposure, yet the mechanisms underlying this vulnerability remain unknown. Studies suggest changes in medial prefrontal cortex (mPFC) activity as a potential contributor. Whether maladaptive changes in inhibitory interneurons participate in this process, and whether adaptations in response to stress differ between men and women, producing sex-specific changes in emotional behaviors and mPFC activity, remained undetermined. This study examined whether unpredictable chronic mild stress (UCMS) in mice differentially alters behavior and mPFC parvalbumin (PV) interneuron activity by sex, and whether the activity of these neurons drives sex-specific behavioral changes. Four weeks of UCMS increased anxiety-like and depressive-like behaviors associated with FosB activation in mPFC PV neurons, particularly in females. After 8 weeks of UCMS, both sexes ...

The cochlear nuclei (CNs) receive sensory information from the ear and perform fundamental computations before relaying this information to higher processing centers. These computations are performed by distinct types of neurons interconnected in circuits dedicated to the specialized roles of the auditory system. In the present study, we explored the use of voltage imaging to investigate CN circuitry. We tested two approaches based on fundamentally different voltage sensing technologies. Using a voltage-sensitive dye we recorded glutamate receptor-independent signals arising predominantly from axons. The mean conduction velocity of these fibers of 0.27 m/s was rapid but in range with other unmyelinated axons. We then used a genetically-encoded hybrid voltage sensor (hVOS) to image voltage from a specific population of neurons. Probe expression was controlled using Cre recombinase linked to c-fos activation. This activity-induced gene enabled targeting of neurons that are activated when a mouse hears a pure...

Comparative neuroimaging allows for the identification of similarities and differences between species. It provides an important and promising avenue, to answer questions about the evolutionary origins of the brain´s organization, in terms of both structure and function. Dog functional magnetic resonance imaging (fMRI) has recently become one particularly promising and increasingly used approach to study brain function and coevolution. In dog neuroimaging, image acquisition has so far been mostly performed with coils originally developed for use in human MRI. Since such coils have been tailored to human anatomy, their sensitivity and data quality is likely not optimal for dog MRI. Therefore, we developed a multichannel receive coil (K9 coil, read “canine”) tailored for high-resolution functional imaging in canines, optimized for dog cranial anatomy. In this paper we report structural ( n  = 9) as well as functional imaging data (resting-state, n  = 6; simple visual paradigm, n  = 9) collected with the K9 c...

Primary cilia are cellular appendages critical for diverse types of singling. They are found on most cell types, including cells throughout the central nervous system. Cilia preferentially localize certain G protein-coupled receptors (GPCRs) and are critical for mediating the signaling of these receptors. Several of these neuronal GPCRs have recognized roles in feeding behavior and energy homeostasis. Cell and model systems like C. elegans and Chlamydomonas have implicated both dynamic GPCR cilia localization and cilia length and shape changes as key for signaling. It is unclear if mammalian ciliary GPCRs utilize similar mechanisms in vivo and under what conditions these processes may occur. Here, we assess two neuronal cilia GPCRs, melanin-concentrating hormone receptor 1 (MCHR1) and neuropeptide-Y receptor 2 (NPY2R), as mammalian model ciliary receptors in the mouse brain. We test the hypothesis that dynamic localization to cilia occurs under physiological conditions associated with these GPCRs’ function...

In females, the hippocampus–a critical brain region for coordination of learning, memory, and behavior–displays altered physiology and behavioral output across the estrous or menstrual cycle. However, the molecular effectors and cell types underlying these observed cyclic changes have only been partially characterized to date. Recently, profiling of mice null for the AMPA receptor trafficking gene Cnih3 have demonstrated estrous-dependent phenotypes in dorsal hippocampal synaptic plasticity, composition, and learning/memory. We therefore profiled dorsal hippocampal transcriptomes from female mice in each estrous cycle stage, and contrasted it with that of males, across wildtype and Cnih3 mutants. In wildtypes, we identified only subtle differences in gene expression between the sexes, while comparing estrous stages to one another revealed up to >1000 differentially expressed genes. These estrous-responsive genes are especially enriched in gene markers of oligodendrocytes and the dentate gyrus, and in funct...

Autoimmune encephalitis (AIE) associated with antibodies directed against the leucine-rich glioma inactivated 1 (LGI1) protein is the second most common autoimmune encephalitis and is responsible for deleterious neocortical and limbic epileptic seizures. Previous studies demonstrated a pathogenic role of anti-LGI1 antibodies via alterations in the expression and function of Kv1 channels and AMPA receptors. However, the causal link between antibodies and epileptic seizures has never been demonstrated. Here, we attempted to determine the role of human anti-LGI1 autoantibodies in the genesis of seizures by analyzing the impact of their intracerebral injection in rodents. Acute and chronic injections were performed in rats and mice in the hippocampus and primary motor cortex, the two main brain regions affected by the disease. Acute infusion of cerebrospinal fluid or serum IgG of anti-LGI1 AIE patients did not lead to the emergence of epileptic activities, as assessed by multisite electrophysiological recordin...

Executive functions arise from multiple regions of the brain acting in concert. To facilitate such cross-regional computations, the brain is organized into distinct executive networks, like the frontoparietal network. Despite similar cognitive abilities across many domains, little is known about such executive networks in birds. Recent advances in avian fMRI have shown a possible subset of regions, including the nidopallium caudolaterale (NCL) and the lateral part of medial intermediate nidopallium (NIML), that may contribute to complex cognition, forming an action control system of pigeons. We investigated the neuronal activity of NCL and NIML. Single-cell recordings were obtained during the execution of a complex sequential motor task that required executive control to stop executing one behavior and continue with a different one. We compared the neuronal activity of NIML to NCL and found that both regions fully processed the ongoing sequential execution of the task. Differences arose from how behavioral...

Sign-tracking (ST) describes the propensity to approach and contact a Pavlovian reward cue. By contrast, goal-trackers (GTs) respond to such a cue by retrieving the reward. These behaviors index the presence of opponent cognitive-motivational traits, with STs exhibiting attentional control deficits, behavior dominated by incentive motivational processes, and vulnerability for addictive drug taking. Attentional control deficits in STs were previously attributed to attenuated cholinergic signaling, resulting from deficient translocation of intracellular choline transporters (CHTs) into synaptosomal plasma membrane. Here we investigated a post-translational modification of CHTs – poly-ubiquitination - and tested the hypothesis that elevated cytokine signaling in STs contributes to CHT modification. We demonstrated that intracellular CHTs, but not plasma membrane CHTs, are highly ubiquitinated in male and female sign-tracking rats when compared with GTs. Moreover, levels of cytokines measured in cortex and str...