Synchronized LFP rhythmicity in the social brain reflects the context of social encounters.

Mammalian social behavior is highly context-sensitive. Yet, little is known about the mechanisms that modulate social behavior according to its context. Recent studies have revealed a network of mostly limbic brain regions which regulates social behavior. We hypothesize that coherent theta and gamma rhythms reflect the organization of this network into functional sub-networks in a context-dependent manner. To test this concept, we simultaneously record local field potential (LFP) from multiple social brain regions in adult male mice performing three social discrimination tasks. While LFP rhythmicity across all tasks is dominated by a global internal state, the pattern of theta coherence between the various regions reflect the behavioral task more than other variables. Moreover, Granger causality analysis implicate the ventral dentate gyrus as a main player in coordinating the context-specific rhythmic activity. Thus, our results suggest that the pattern of coordinated rhythmic activity within the network reflects the subject's social context.

The role of the prefrontal cortex in social interactions of animal models and the implications for autism spectrum disorder.

Social interaction is a complex behavior which requires the individual to integrate various internal processes, such as social motivation, social recognition, salience, reward, and emotional state, as well as external cues informing the individual of others' behavior, emotional state and social rank. This complex phenotype is susceptible to disruption in humans affected by neurodevelopmental and psychiatric disorders, including autism spectrum disorder (ASD). Multiple pieces of convergent evidence collected from studies of humans and rodents suggest that the prefrontal cortex (PFC) plays a pivotal role in social interactions, serving as a hub for motivation, affiliation, empathy, and social hierarchy. Indeed, disruption of the PFC circuitry results in social behavior deficits symptomatic of ASD. Here, we review this evidence and describe various ethologically relevant social behavior tasks which could be employed with rodent models to study the role of the PFC in social interactions. We also discuss the evidence linking the PFC to pathologies associated with ASD. Finally, we address specific questions regarding mechanisms employed by the PFC circuitry that may result in atypical social interactions in rodent models, which future studies should address.

Modular Electrode Array for Multi-site Extracellular Recordings from Brains of Freely Moving Rodents.

Multi-site extracellular recordings from awake, freely moving rodents are an insightful technique that allows deduction of the dynamics of neural activity within a network of brain regions. Multiple advances in the design and materials of recording setups are available in the literature. However, most of these designs require several skill sets to assemble the electrodes and are expensive. Here, we explain in detail a custom design to build a multi-site (16 sites) electrode array (EA) and record extracellular electrical signals (local field potential and multi-unit spiking activity) at variable depths in freely behaving rodents. This EA weighs ∼3.0 g and costs less than $30. It provides mesoscopic neural activity maps (at millimeter scale) at low spatial resolution, thus enabling the experimenting group to further target specific regions with more expensive high-density probes at the resolution of an individual neuron. The article outlines the processes of building and implanting the array and recording neural activity during a behavior task. We also highlight the limitations of our design and the necessary steps to troubleshoot common issues faced during the initial implementation of the protocols. Finally, we explain the specific data one would obtain while using the probes during social interactions between rodents. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Preparation of the electrode array Basic Protocol 2: Surgical implantation of the electrode array Basic Protocol 3: Recording of neural activity from the electrode array while a mouse performs social investigation of a novel conspecific Basic Protocol 4: Histology and electrode registration.

Distinct Dynamics of Theta and Gamma Rhythmicity during Social Interaction Suggest Differential Mode of Action in the Medial Amygdala of Sprague Dawley Rats and C57BL/6J Mice.

The medial nucleus of the amygdala (MeA) is known to regulate social behavior. This brain area is functionally positioned in a crossroads between sensory information processing and behavioral modulation. On the one hand, it receives direct chemosensory input from the accessory olfactory bulb. On the other hand, it orchestrates various behavioral outputs via brain-wide projections under the regulation of multiple neuromodulatory systems. Previously, we showed that adult male Sprague Dawley (SD) rats and C57BL/6J mice, the most widely used rodent models in neuroscience research, differ in their dynamics of motivation to interact with a novel same-sex conspecific and that this difference correlates with the level of c-Fos expression in the MeA. Here we used chronically implanted electrodes to compare rhythmic local field potential signals recorded from these animals during free and restricted social interactions. We found a significant induction of rhythmicity in the theta (4-12 Hz) and gamma (30-80 Hz) bands during both free and restricted social interaction in both rats and mice. However, the induction of gamma rhythmicity, thought to reflect activity of local neuronal networks, was significantly higher in rats than mice. Nevertheless, in contrast to rats, mice exhibited induction of rhythmicity, in both the theta and gamma bands, in synchrony with investigation of social, but not object stimuli. These results suggest that during interaction with a novel same-sex conspecific, the MeA of C57BL/6J mice is mostly involved in sensory information processing while in SD rats it is mainly active in modulating the social motivation state of the animal.

Investigating Behavioral Responses to Mirrors and the Mark Test in Adult Male Zebra Finches and House Crows.

Earlier evidence suggests that besides humans, some species of mammals and birds demonstrate visual self-recognition, assessed by the controversial "mark" test. Whereas, there are high levels of inter-individual differences amongst a single species, some species such as macaques and pigeons which do not spontaneously demonstrate mirror self-recognition (MSR) can be trained to do so. We were surprised to discover that despite being widely used as a model system for avian research, the performance of zebra finches (Taenopygia guttata) on the mark test had not been studied earlier. Additionally, we studied the behavioral responses of another species of passerine songbirds (Indian house crows; Corvus splendens) to a mirror and the MSR mark test. Although a small number of adult male zebra finches appeared to display heightened responses toward the mark while observing their reflections, we could not rule out the possibility that these were a part of general grooming rather than specific to the mark. Furthermore, none of the house crows demonstrated mark-directed behavior or increased self-exploratory behaviors when facing mirrors. Our study suggests that self-directed behaviors need to be tested more rigorously in adult male zebra finches while facing their reflections and these findings need to be replicated in a larger population, given the high degree of variability in mirror-directed behaviors.

Blocking Opioid Receptors in a Songbird Cortical Region Modulates the Acoustic Features and Levels of Female-Directed Singing.

The organization of the anterior forebrain pathway (AFP) of songbirds important for context-dependent singing is similar to that of cortical basal ganglia loops (CBG) in mammals, which underlie motor behaviors including vocalization. Since different components of the AFP express high levels of µ-opioid receptors (µ-ORs) as do CBG loops, songbirds act as model systems to study the role of opioid modulation on vocalization and the motivation to sing. The AFP in songbirds includes the cortical/pallial region LMAN (lateral magnocellular nucleus of the anterior nidopallium) which projects to Area X, a nucleus of the avian basal ganglia. In the present study, microdialysis was used to infuse different doses of the opioid antagonist naloxone in LMAN of adult male zebra finches. Whereas all doses of naloxone led to significant decreases in the number of FD (female-directed) songs, only 100 and 200 ng/ml of naloxone affected their acoustic properties. The decrease in FD song was not accompanied by changes in levels of attention toward females or those of neurotransmitters (dopamine, glutamate, and GABA) in LMAN. An earlier study had shown that similar manipulations in Area X did not lead to alterations in the number of FD songs but had significantly greater effects on their acoustic properties. Taken together, our results suggest that there are reciprocal effects of OR modulation on cortical and basal ganglia components of the AFP in songbirds.

A community-based transcriptomics classification and nomenclature of neocortical cell types.

To understand the function of cortical circuits, it is necessary to catalog their cellular diversity. Past attempts to do so using anatomical, physiological or molecular features of cortical cells have not resulted in a unified taxonomy of neuronal or glial cell types, partly due to limited data. Single-cell transcriptomics is enabling, for the first time, systematic high-throughput measurements of cortical cells and generation of datasets that hold the promise of being complete, accurate and permanent. Statistical analyses of these data reveal clusters that often correspond to cell types previously defined by morphological or physiological criteria and that appear conserved across cortical areas and species. To capitalize on these new methods, we propose the adoption of a transcriptome-based taxonomy of cell types for mammalian neocortex. This classification should be hierarchical and use a standardized nomenclature. It should be based on a probabilistic definition of a cell type and incorporate data from different approaches, developmental stages and species. A community-based classification and data aggregation model, such as a knowledge graph, could provide a common foundation for the study of cortical circuits. This community-based classification, nomenclature and data aggregation could serve as an example for cell type atlases in other parts of the body.

Altering Opioid Neuromodulation in the Songbird Basal Ganglia Modulates Vocalizations.

Although the interplay between endogenous opioids and dopamine (DA) in the basal ganglia (BG) is known to underlie diverse motor functions, few studies exist on their role in modulating speech and vocalization. Vocal impairment is a common symptom of Parkinson's disease (PD), wherein DA depletion affects striosomes rich in µ-opioid receptors (µ-ORs). Symptoms of opioid addiction also include deficiencies in verbal functions and speech. To understand the interplay between the opioid system and BG in vocalization, we used adult male songbirds wherein high levels of µ-ORs are expressed in Area X, a BG region which is part of a circuit similar to the mammalian thalamocortical-basal ganglia loop. Changes in DA, glutamate and GABA levels were analyzed during the infusion of different doses of the µ-OR antagonist naloxone (50 and 100 ng/ml) specifically in Area X. Blocking µ-ORs in Area X with 100 ng/ml naloxone led to increased levels of DA in this region without altering the number of songs directed toward females (FD). Interestingly, this manipulation also led to changes in the spectro-temporal properties of FD songs, suggesting that altered opioid modulation in the thalamocortical-basal ganglia circuit can affect vocalization. Our study suggests that songbirds are excellent model systems to explore how the interplay between µ-ORs and DA modulation in the BG affects speech/vocalization.

Contusive spinal cord injury up regulates mu-opioid receptor (mor) gene expression in the brain and down regulates its expression in the spinal cord: possible implications in spinal cord injury research.

Traumatic spinal cord injury (SCI) is one of the dreaded neurological conditions and finding a cure for it has been a hot area of research. Naloxone - a mu-opiate receptor (mor) antagonist was considered for SCI treatment based on its positive effects under shock conditions. In contrary to animal studies based reports about the potential benefits of naloxone in treating SCI, a large scale clinical trial [National Acute Spinal Cord Injury Study II (NASCIS II)] conducted in USA failed to witness any effectiveness. The inconsistency noticed was intriguing. Therefore, the objective of the present study was to re-examine the role of naloxone in treating SCI using a highly standardised Multicenter Animal Spinal Cord Injury Study (MASCIS) animal model of contusive SCI. Results indicated that naloxone produced negligible and insignificant neuroprotection. In an attempt to understand the cause for the failure, it was found that mu-opioid receptor (mor) gene expression was upregulated in the brain but was down regulated in the spinal cord after contusive SCI. Given that the beneficial effects of naloxone are through its action on the mor, the results indicate that unlike the brain, spinal cord might not be bracing to utilise the opiate system in the repair process. This could possibly explain the failure of naloxone treatment in NASCIS II. To conclude, opiate antagonists like naloxone may be neuroprotective for treating traumatic brain injuries, but not for traumatic/contusive spinal cord injuries.