Summary: A recent study has uncovered that parvalbumin-positive interneurons (PV interneurons) serve as critical regulators in the brain’s social circuitry. When researchers suppressed PV interneurons in mice, the animals no longer prioritized social targets or displayed consoling behavior suggesting these neurons act as switches that guide social decision-making and emotional recognition. When researchers removed these neurons from mice, the mice could no longer distinguish between familiar and unfamiliar companions and showed no preference for their distressed companions.
Researchers have uncovered a pivotal role for PV interneurons in regulating social behavior, acting as dynamic switches within neural circuits that guide how animals select their social interactions. These specialized cells appear to fine-tune the brain’s response to social cues, shaping decisions about whom to engage with and when.
This discovery opens new avenues for understanding the neural basis of psychiatric conditions such as autism and schizophrenia. Both disorders have been linked to disruptions in PV interneuron function, suggesting that these cells may hold the key to decoding the social impairments often seen in affected individuals.
Key data
- Social Switching Cell: PV interneurons control whether animals show empathy or recognize familiar stimuli.
- Effects on behavior: Restrained rats treated strangers and conspecifics equally and ignored stressed rats.
- Medical relevance: Abnormalities of these cells are also seen in autism and schizophrenia.
Source: Kobe University
Social interactions involve many decisions: How much time do we spend with a friend? Should we prioritize spending time with a friend who seems down?
As with all behaviors, specific groups of neurons in the brain are responsible for processing these complex behaviors. Developmental disorders in these areas are associated with neuropsychiatric disorders such as autism spectrum disorders or schizophrenia.
Kobe University neuroscientist Takumi Toro has long been researching the neurological basis of these diseases.
He explains that “their earlier research had pinpointed a set of neurons in mice that become active during social engagement. Building on that, the team aimed to investigate the function of a particular type of signal-regulating cell known as PV interneurons—cells they were aware of but had not yet fully understood in the context of social behavior”.
Takumi’s team achieved a remarkable feat by implanting an endoscopic camera into the brains of genetically modified mice, allowing them to observe neural activity as it unfolded in real time. This innovative technique enabled the researchers to track which neurons lit up during specific behaviors, offering unprecedented insight into the brain’s decision-making and social processing mechanisms.
Furthermore, they introduced genetic changes that allowed them to specifically reduce the activity of targeted neurons.
In the journal Cell Reports, neuroscientists from Kobe University, in collaboration with Sato Masaki from the Kyoto Institute of Technology, now report that mice whose PV interneurons were inhibited showed two interesting behavioral features.
First, they failed to get to know their companions. Normal mice spend less time with familiar individuals than with strangers they meet for the first time. In contrast, mice with inhibited PV interneurons spend just as much time with their companions as with strangers.
Second, when given a choice between two specific objects—a stressful and a non-stressful one—normal rats spent more time with the stressful one. In contrast, restrained rats did not exhibit this comforting behavior.
“Our results show for the first time that these specialized cells act as switches in the ‘social cell’ network to control empathic behavior,” explains Takumi.
In a separate experiment in which rats were allowed to interact freely with individuals they were meeting for the first time, the restrained rats showed no difference from normal rats.
This suggests that the role of PV interneurons is not so much associated with social behavior in general, but rather with the modulation of preference for social goals and thus decision-making in social matters.
Takumi underscores the broader impact of the study, describing it as a pivotal step toward decoding the neural architecture that underlies human social behavior. By revealing how specific brain cells influence social decision-making and emotional recognition, the research offers valuable insights into the biological roots of empathy, connection, and social cognition.
By identifying how specific brain cells influence social interactions, the study lays the groundwork for deeper insights into empathy, connection, and the mechanisms behind social disorders.
PV interneuron abnormalities have previously been observed in animal models and in patients with autism spectrum disorders and schizophrenia. Future comparative studies between mice and humans may lead to new insights.”
Funding: This research was supported by the Japan Society for the Promotion of Science (Grants 23K27359, 24H02315, 23K14673, 24H00904, 23H04233, 23KK0132, 24K22036, 24H22036, 24H02042), the Japan Agency for Medical Research and Development (Grant JP21wm0425011), the Japan Science and Technology Agency (Grants JPMJMS2299, JPMJMS229B), the National Center for Neurology and Psychiatry (Grants 6-9), the Takeda Science Foundation, and the Taiju Life Welfare Foundation. The study was carried out in close collaboration with researchers from Hokkaido University and the Kyoto Institute of Technology, combining expertise across institutions to deepen insights into the neural mechanisms of social behavior. This interdisciplinary partnership played a key role in advancing the research and broadening its scientific impact.
Abstract
Recent findings highlight the pivotal role of parvalbumin-positive interneurons (PV interneurons) within the insular cortex in regulating social behavior and emotional awareness. These specialized inhibitory neurons act as modulators, helping the brain distinguish between familiar and unfamiliar individuals and respond appropriately to emotional cues. Their activity appears to guide social orientation, such as whom to approach or avoid and influence how empathy is expressed, offering new insights into the neural basis of conditions like autism and schizophrenia.
Although the insular cortex is known to be central to various social behaviors, the mechanisms behind its inhibitory regulation have remained elusive. By using advanced imaging and genetic tools, scientists are now beginning to uncover how PV interneurons fine-tune social familiarity and empathy—offering new insights into conditions like autism and schizophrenia, where dysfunction in these cells has been observed.
Using cell-type-specific microendoscopic calcium imaging and chemogenetic manipulation of neuronal activity, we discovered that parvalbumin-positive interneurons (PVINs) in the agranular insular cortex (aIC) are important for the control of social orientation and emotion recognition.
Similar to pyramidal neurons (PNs), a specific subset of PVINs showed increased activity during peer interaction.
Inhibition of PVIN resulted in preservation of preference for familiar companions and decreased interactions with stressed individuals.
These behavioral changes were related to changes in the proportion of PNs who performed activities with interactions with significant peers, as well as shifts in the specificity of their social goals between sessions.
Our results highlight that PVINs provide context-dependent control over socioemotional behavior and the encoding of social information to locally adjust the social preference of individual PNs in the AIC.
