CoChat
Sign Up
Cited by 21Neuroendocrine regulation and behaviorNeuroscience and Neuropharmacology ResearchMemory and Neural Mechanisms

Social Interaction Elicits Activity in Glutamatergic Neurons in the Posterior Intralaminar Complex of the Thalamus

Open access
Leithead, Amanda Beth, Godino, Arthur, Barbier, Marie, Harony-Nicolas, Hala·2024·Biological Psychiatry
DOI 10.1016/j.biopsych.2023.05.016PMC PMC10676449
Open this paper in CoChat — free accountOpen PDF

Abstract

BACKGROUND: The posterior intralaminar complex of the thalamus (PIL) is a multimodal nucleus that has been implicated in maternal behaviors and conspecific social behaviors in male and female rodents. Glutamatergic neurons are a major component of the PIL; however, their specific activity and role during social interactions has not yet been assessed. METHODS: We used immunohistochemistry for the immediate early gene c-fos as a proxy for neuronal activity in the PIL of mice exposed to a novel social stimulus, a novel object stimulus, or no stimulus. We then used fiber photometry to record neural activity of glutamatergic neurons in the PIL in real time during social and nonsocial interactions. Finally, we used inhibitory DREADDs (designer receptors exclusively activated by designer drugs) in glutamatergic PIL neurons and tested social preference and social habituation-dishabituation. RESULTS: We observed significantly more c-fos-positive cells in the PIL of mice exposed to a social stimulus versus an object stimulus or no stimulus. Neural activity of PIL glutamatergic neurons was increased when male and female mice were engaged in social interaction with a same-sex juvenile or opposite-sex adult, but not a toy mouse. Neural activity was positively correlated with social investigation bout length and negatively correlated with chronological order of bouts. Social preference was unaffected by inhibition; however, inhibiting activity of glutamatergic neurons in the PIL delayed the time that it took for female mice to form social habituation. CONCLUSIONS: Together, these findings suggest that glutamatergic PIL neurons respond to social stimuli in both male and female mice and may regulate perceptual encoding of social information to facilitate recognition of social stimuli.

AI snapshot

Written from the paper’s full text.

TL;DR

Glutamatergic neurons in the posterior intralaminar complex of the thalamus (PIL) are activated by novel social stimuli in male and female mice, but not by a novel object. Inhibiting these neurons does not block social preference and delays social habituation in females, suggesting a role in perceptual encoding or recognition of social stimuli.

Key findings

  • c-fos+ cells in the PIL were higher after social interaction (M = 485, SD = 64.64) than after object (M = 385.1, SD = 41.42) or no stimulus (M = 233.2, SD = 51.52; F(2,11) = 28.52, p < .0001; n = 3/sex/condition).
  • Fiber photometry showed increased activity of PIL glutamatergic neurons during same-sex juvenile interaction (AUC before M = −0.06, SD = 1.26 to during M = 1.51, SD = 2.11; F(1,13) = 10.68, p = .006) and opposite-sex adult interaction (before M = 0.19, SD = 1.46 to during M = 1.78, SD = 1.54; F(1,13) = 24.08, p < .001), but not during object interaction (p = .747).
  • Peak neural activity positively correlated with investigation bout length for same-sex juvenile (beta = 0.032, t(221.3) = 3.93, p < .001) and opposite-sex adult (beta = 0.019, t(200.3) = 3.88, p < .001), and negatively correlated with chronological bout order for same-sex juvenile (beta = −0.069, t(220.2) = −3.59, p < .001) and opposite-sex adult (beta = −0.066, t(203.4) = −3.70, p < .001).
  • Inhibitory DREADDs did not affect social preference for same-sex juvenile (treatment p = .956) or opposite-sex adult (treatment p = .096), but in females CNO delayed social habituation: higher investigation ratio at T2 (CNO M = 1.22, SD = 0.61 vs vehicle M = 0.83, SD = 0.35; t(24) = 2.91, p = .03) and T3 (CNO M = 1.25, SD = 0.64 vs vehicle M = 0.73, SD = 0.28; t(24) = 3.92, p = .003), but not T4 (p = .799).

Methods

  • Adult male and female C57BL/6 mice (8–12 weeks) were used; social stimuli were same-sex juveniles (4–5 weeks) or opposite-sex adults (8–12 weeks), with a toy mouse as object control.
  • c-fos immunohistochemistry followed 1-hour free interaction with social, object, or no stimulus; fiber photometry used CaMKIIα-Cre + Cre-dependent GCaMP6m to record glutamatergic PIL activity during social/object preference tasks; inhibitory DREADDs (hM4D(Gi)) with CNO (3.5 mg/kg IP) or vehicle were tested in social preference and social habituation-dishabituation.
  • Analyses included ANOVAs, mixed models, and linear mixed models; sample sizes were not predetermined by power analysis but chosen to match previous publications.

Limitations

  • Stated: no statistical power estimation was used; sample sizes were chosen to match prior publications.
  • Stated: male mice did not show habituation even with vehicle, so effects of CNO in males were inconclusive, possibly due to increased aggressive behavior; social recognition was eventually achieved in females on T4, suggesting other neurons or regions can compensate.
  • Evident: c-fos experiments used n = 3/sex/condition, and fiber photometry/DREADD analyses had exclusions for viral expression, fiber placement, or aggression; the fiber photometry arena allowed auditory, visual, and olfactory but not somatosensory/touch information.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.biopsych.2023.05.016

Cites

51 of 51 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

0 of 53 cited sources checked · 0 supported · 0 flagged

  • Findingown data
    § Chemogenetic inactivation of glutamatergic PIL neurons delays the formation of social recognition in females

    Female mice displayed a higher investigation ratio to the first interaction at T2 under CNO versus vehicle.

    “such that female mice displayed a higher investigation ratio to the first interaction at T2 under CNO (M = 1.22, SD = 0.61) versus vehicle (M = 0.83, SD = 0.35; t(24) = 2.91, p = 0.03)”
    Quote in the paperSubstantial claim
  • Findingown data
    § Chemogenetic inactivation of glutamatergic PIL neurons does not affect social preference in males and females

    In the adult social preference task, there was no effect of treatment on the discrimination index.

    “Additionally, there was no effect of treatment on the discrimination index (p = .16; Fig. 4I).”
    Quote in the paperSubstantial claim
  • Findingown data
    § Real-time activity of glutamatergic PIL neurons increases during novel same-sex and opposite-sex social interactions, but not novel object interaction

    There was no significant difference in investigation time between the compartment containing a moving toy mouse and the empty compartment.

    “However, there was no significant difference in investigation time between the compartment containing a moving toy mouse versus empty (p = .341; Fig. 2B, lower panel yellow).”
    Quote in the paperSubstantial claim
  • Findingown data
    § Chemogenetic inactivation of glutamatergic PIL neurons does not affect social preference in males and females

    In the adult social preference task, males and females preferred the opposite-sex adult to the empty chamber.

    “Similarly, in the adult social preference task, males and females preferred the opposite-sex adult to the empty chamber (F(1,11) = 40.33, p &lt; .0001);”
    Quote in the paperNot a substantial claim
  • Findingown data
    § Real-time activity of glutamatergic PIL neurons increases during novel same-sex and opposite-sex social interactions, but not novel object interaction

    The average area under the curve of GcaMP6m signals significantly increased from before to during investigation of a same-sex juvenile.

    “The average area under the curve significantly increased in response to the same-sex juvenile from before (M = -0.06, SD = 1.26) to during investigation (M = 1.51, SD = 2.11; F(1, 13) = 10.68, p = .006; Fig. 2E blue).”
    Quote in the paperSubstantial claim
  • May combine two claims. 19
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 14

  • May combine two claims. The quote only partly states this claim.

    Findingown data
    § Chemogenetic inactivation of glutamatergic PIL neurons delays the formation of social recognition in females

    In male mice, there was no effect of CNO/vehicle treatment on total investigation time on T1 or T5.

    “Furthermore, we found no effect of CNO/vehicle treatment on the total investigation time on T1 (p = .066; Fig. 5C) or on T5 (p = .684; Fig. 5D).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Chemogenetic inactivation of glutamatergic PIL neurons delays the formation of social recognition in females

    In male mice, there were no significant changes in investigation ratio over time (T1-T4) or between treatments in the social habituation-dishabituation task.

    “Using this task in male mice, we found no significant changes in investigation ratio over time (T1-T4, p = .067) or between treatments (T1-T4, p = .607) (Fig. 5B)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Chemogenetic inactivation of glutamatergic PIL neurons delays the formation of social recognition in females

    In female mice, there was an effect of time over T1-T4 and a significant interaction between time and treatment in the social habituation-dishabituation task.

    “However, in female mice, there was an effect of time over T1-T4 (F(3,24) = 3.31, p = .037) with a significant interaction between time and treatment (F(3,24) = 3.17, p = .043)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Chemogenetic inactivation of glutamatergic PIL neurons delays the formation of social recognition in females

    Female mice displayed a higher investigation ratio at T3 under CNO versus vehicle, but not at T4.

    “and at T3 under CNO (M = 1.25, SD = 0.64) versus vehicle (M = 0.73, SD = 0.28; t(24) = 3.92, p = 0.003) but not at T4 (p = .799; Fig. 5E).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Chemogenetic inactivation of glutamatergic PIL neurons delays the formation of social recognition in females

    There was no difference in investigation time between CNO/vehicle treatment groups in response to the novel mouse at T1 or the final novel mouse in female mice.

    “Additionally, there was no difference in investigation time between CNO/vehicle treatment groups in response to the novel mouse at T1 (p = .876; Fig. 5F) or the final novel mouse (p = .694; Fig. 5G).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Abstract

    GcaMP6m signals in PIL glutamatergic neurons increased during interaction with novel same-sex or novel opposite-sex stimuli, but not during interaction with a novel object.

    “Neural activity of PIL glutamatergic neurons was increased when male and female mice were engaged in social interaction with a same-sex juvenile or opposite-sex adult, but not a toy mouse.”
    • Also stated in: § Real-time activity of glutamatergic PIL neurons increases during novel same-sex and opposite-sex social interactions, but not novel object interaction · plain
      “We observed that GcaMP6m signals increased during interaction with novel same-sex or novel opposite sex stimuli, but not during interaction with a novel object (Fig. 2D).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § REFERENCES

    Inhibiting glutamatergic neurons in the PIL delays social recognition in females but not in males.

    “Inhibiting glutamatergic neurons in the PIL delays social recognition in females but not in males.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § REFERENCES

    Activity of PIL glutamatergic neurons (measured as AUC of GCaMP signal) is increased during same-sex and opposite-sex social interactions, but not object interaction, in male and female mice.

    “Activity of PIL glutamatergic neurons is increased during same-sex and opposite-sex social interactions, but not object interaction, in males and females.”
    • Also stated in: § REFERENCES · plain
      “The area under the curve (AUC), calculated from average standardized traces, significantly increased during investigation of same-sex juvenile and opposite-sex adult stimuli, but not object”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § DISCUSSION

    Oxytocin has a well-established role in social behaviors and social recognition.

    “and the well-established role of oxytocin in social behaviors and social recognition (13, 21, 34; 39-44).”
    Quote in the paperNot a substantial claim0 of 9 sources checked
    • cites [13] Bielsky, 2004, Oxytocin, vasopressin, and social recognition in mammals, Peptides source

      Not checked in the free run.

    • cites [21] Ferguson, 2000, Social amnesia in mice lacking the oxytocin gene, Nat Genet source

      Not checked in the free run.

    • cites [34] Insel, 2004, How the Brain processes social information: Searching for the social brain, Annu Rev Neurosci source

      Not checked in the free run.

    • cites [39] Lin, 2018, Conditional deletion of hippocampal CA2/CA3a oxytocin receptors impairs the persistence of long-term social recognition memory in mice, J Neurosci source

      Not checked in the free run.

    • cites [40] Lukas, 2013, Oxytocin mediates rodent social memory within the lateral septum and the medial amygdala depending on the relevance of the social stimulus: Male juvenile versus female adult conspecifics, Psychoneuroendocrinology source

      Not checked in the free run.

    • cites [41] Penn, 2010, Kin recognition: An overview of conceptual issues, mechanisms and evolutionary theory

      Not checked in the free run.

    • cites [42] Popik, 1992, Low doses of oxytocin facilitate social recognition in rats, Psychopharmacology source

      Not checked in the free run.

    • cites [43] Raam, 2017, Hippocampal oxytocin receptors are necessary for discrimination of social stimuli, Nat Commun source

      Not checked in the free run.

    • cites [44] Takayanagi, 2005, Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice, Proc Natl Acad Sci USA source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § INTRODUCTION

    In maternal female rats, a subpopulation of PIL neurons expressing TIP39 is activated in response to pup exposure and suckling.

    “In maternal female rats, a subpopulation of PIL neurons that expresses tuberoinfundibular peptide 39 (TIP39) were shown to be activated in response to pup exposure and suckling (2-4).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [2] Cservenák, 2010, Tuberoinfundibular peptide of 39 residues is activated during lactation and participates in the suckling-induced prolactin release in rat, Endocrinology source

      Not checked in the free run.

    • cites [3] Cservenák, 2017, A thalamo-hypothalamic pathway that activates oxytocin neurons in social contexts in female rats, Endocrinology source

      Not checked in the free run.

    • cites [4] Cservenák, 2013, Thalamic neuropeptide mediating the effects of nursing on lactation and maternal motivation, Psychoneuroendocrinology source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § INTRODUCTION

    The PIL has been shown to be involved in grooming behavior in males and females.

    “and more recently, shown to be involved in grooming behavior in males and females (11).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11] Keller, 2022, A thalamo-preoptic pathway promotes social grooming in rodents, Curr Biol source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation
    § INTRODUCTION

    The PIL is considered a relay center by which sensory information is conveyed to other brain regions for the generation of relevant social behaviors.

    “The posterior intralaminar complex of the thalamus (PIL) is considered a relay center by which sensory information is conveyed to other brain regions for the generation of relevant social behaviors (1-6).”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [1] Dobolyi, 2018, Thalamic integration of social stimuli regulating parental behavior and the oxytocin system, Front Neuroendocrinol source

      Not checked in the free run.

    • cites [2] Cservenák, 2010, Tuberoinfundibular peptide of 39 residues is activated during lactation and participates in the suckling-induced prolactin release in rat, Endocrinology source

      Not checked in the free run.

    • cites [3] Cservenák, 2017, A thalamo-hypothalamic pathway that activates oxytocin neurons in social contexts in female rats, Endocrinology source

      Not checked in the free run.

    • cites [4] Cservenák, 2013, Thalamic neuropeptide mediating the effects of nursing on lactation and maternal motivation, Psychoneuroendocrinology source

      Not checked in the free run.

    • cites [5] Hansen, 1984, The importance of the peripeduncular nucleus in the neuroendocrine control of sexual behavior and milk ejection in the rat, Neuroendocrinology source

      Not checked in the free run.

    • cites [6] Factor, 1993, Peripeduncular nucleus lesions in the rat: I. Effects on maternal aggression, lactation, and maternal behavior during pre- and postpartum periods, Behav Neurosci source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning
    § DISCUSSION

    Together, results from rat and mouse studies suggest that the PIL plays a role in processing sensory inputs, although the specific neural pathways involved may differ depending on species, sex, and behavioral context.

    “Together, the results from rat and mouse studies suggest that the PIL plays a role in processing sensory inputs, although the specific neural pathways involved may differ depending on the species, sex, and behavioral context.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § INTRODUCTION

    Oxytocin neurons in the PVH regulate a range of social behaviors, from parental care to social recognition of conspecifics.

    “which are known to regulate a range of social behaviors, from parental care to social recognition of conspecifics (13-18).”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [13] Bielsky, 2004, Oxytocin, vasopressin, and social recognition in mammals, Peptides source

      Not checked in the free run.

    • cites [14] Donaldson, 2008, Oxytocin, vasopressin, and the neurogenetics of sociality, Science source

      Not checked in the free run.

    • cites [15] Ferguson, 2002, The neuroendocrine basis of social recognition, Front Neuroendocrinol source

      Not checked in the free run.

    • cites [16] Insel, 2001, The neurobiology of attachment, Nat Rev Neurosci source

      Not checked in the free run.

    • cites [17] Insel, 2000, Neuropeptides and the evolution of social behavior, Curr Opin Neurobiol source

      Not checked in the free run.

    • cites [18] Froemke, 2021, Oxytocin, neural plasticity, and social behavior, Annu Rev Neurosci source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data
    § DISCUSSION

    Inhibition of glutamatergic PIL neurons delayed the time to habituation, suggesting a delay in social recognition.

    “However, we found that inhibition of glutamatergic PIL neurons delayed the time to habituation (CNO treatment led to a higher ratio of investigation at T2 and T3), suggesting a delay in social recognition.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S1 (asserted). May combine two claims.

    Premisecitation
    § Novel social interaction elicits c-fos activation in the PIL

    Excitatory projections from the PIL to the PVH are involved in social interactions in females and may contribute to oxytocin release via direct inputs to oxytocin cells.

    “Previous research has suggested that excitatory projections from the PIL to the PVH are involved in social interactions in females and may contribute to oxytocin release via direct inputs to oxytocin cells (3).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [3] Cservenák, 2017, A thalamo-hypothalamic pathway that activates oxytocin neurons in social contexts in female rats, Endocrinology source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisereasoning
    § DISCUSSION

    It has been suggested that sensory information from pups during maternal reflexes and behavior is conveyed to the MPOA and PVH of lactating mothers through the PIL→MPOA and/or PIL→PVH pathways.

    “it has been suggested that sensory information from pups during maternal reflexes and behavior is conveyed to the MPOA and PVH of the lactating mothers through the PIL ➔ MPOA and/or PIL ➔ PVH pathways.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data
    § DISCUSSION

    Glutamatergic neurons of the PIL are not the only player in encoding social sensory and/or somatosensory information during social recognition; other neuronal populations of the PIL and/or brain regions may be involved and can eventually compensate for the lack of PIL glutamatergic activity, yet with some delay.

    “indicates that glutamatergic neurons of the PIL are not the only player in encoding social sensory and/or somatosensory information during social recognition and that other neuronal populations of the PIL and/or brain regions may be involved and can eventually compensate for the lack of PIL glutamatergic activity, yet with some delay.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § INTRODUCTION

    These TIP39 neurons co-express calbindin and VGlut2 and form presumed excitatory synapses with oxytocin neurons in the PVH.

    “These neurons co-express calbindin and vesicular glutamate transporter 2 (VGlut2), and form presumed excitatory synapses with oxytocin neurons in the PVH (3, 12)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [3] Cservenák, 2017, A thalamo-hypothalamic pathway that activates oxytocin neurons in social contexts in female rats, Endocrinology source

      Not checked in the free run.

    • cites [12] Tang, 2020, Social touch promotes interfemale communication via activation of parvocellular oxytocin neurons, Nat Neurosci source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § DISCUSSION

    Glutamatergic circuits within the hypothalamus play a role in the release of oxytocin.

    “given the role of glutamatergic circuits within the hypothalamus in the release of oxytocin (52)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [52] Leithead, 2021, The interplay between glutamatergic circuits and oxytocin neurons in the hypothalamus and its relevance to neurodevelopmental disorders, J Neuroendocrinol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § DISCUSSION

    A recent study in mice identified a population of SPFp neurons expressing CGRP that respond to multi-sensory threat stimuli and project to the lateral amygdala to regulate fear memory.

    “A recent study conducted in mice focused on the subparafascicular nucleus (SPFp), which shares neuroanatomical borders with the PIL, and identified a population of SPFp neurons that express calcitonin gene-related peptide (CGRP). This study revealed that CGRP expressing neurons respond to multi-sensory threat stimuli and project to the lateral amygdala to regulate fear memory (26).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [26] Kang, 2022, A central alarm system that gates multi-sensory innate threat cues to the amygdala, Cell Rep source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § INTRODUCTION

    Tracing studies in rodents have shown that the PIL receives inputs from sensory regions such as the inferior and superior colliculus, auditory cortex, and spinal cord and projects to socially relevant brain regions including the PVH, lateral septum, MPOA, and medial amygdala.

    “Tracing studies conducted in rodents have provided anatomical support for this theory, demonstrating that the PIL receives inputs from sensory regions such as the inferior and superior colliculus, auditory cortex, and spinal cord (3, 7-10) and projects to socially relevant brain regions including the paraventricular nucleus of the hypothalamus (PVH), the lateral septum, medial preoptic area (MPOA)”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [3] Cservenák, 2017, A thalamo-hypothalamic pathway that activates oxytocin neurons in social contexts in female rats, Endocrinology source

      Not checked in the free run.

    • cites [7] Cai, 2019, Distinct anatomical connectivity patterns differentiate subdivisions of the nonlemniscal auditory thalamus in mice, Cereb Cortex source

      Not checked in the free run.

    • cites [8] Ledoux, 1987, Topographic organization of convergent projections to the thalamus from the inferior colliculus and spinal cord in the rat, J Comp Neurol source

      Not checked in the free run.

    • cites [9] Linke, 1999, Differential projection patterns of superior and inferior collicular neurons onto posterior paralaminar nuclei of the thalamus surrounding the medial geniculate body in the rat, Eur J Neurosci source

      Not checked in the free run.

    • cites [10] Yasui, 1990, The subparafascicular thalamic nucleus of the rat receives projection fibers from the inferior colliculus and auditory cortex, Brain Res source

      Not checked in the free run.

    • cites [11] Keller, 2022, A thalamo-preoptic pathway promotes social grooming in rodents, Curr Biol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data
    § Fiber Photometry Recording

    Subjects were excluded from fiber photometry analyses based on lack of viral expression or fiber misplacement observed upon postmortem inspection.

    “Subjects were excluded from analyses based on lack of viral expression (n = 2 males) or fiber misplacement observed upon postmortem inspection of the injection site (n = 1 male, 2 females).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given
    § Novel social interaction elicits c-fos activation in the PIL

    No statistical power estimation analyses were used to predetermine sample sizes; sample sizes were chosen to match previous publications.

    “No statistical power estimation analyses were used to predetermine sample sizes, which instead were chosen to match previous publications (2, 11, 26-28).”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [2] Cservenák, 2010, Tuberoinfundibular peptide of 39 residues is activated during lactation and participates in the suckling-induced prolactin release in rat, Endocrinology source

      Not checked in the free run.

    • cites [11] Keller, 2022, A thalamo-preoptic pathway promotes social grooming in rodents, Curr Biol source

      Not checked in the free run.

    • cites [26] Kang, 2022, A central alarm system that gates multi-sensory innate threat cues to the amygdala, Cell Rep source

      Not checked in the free run.

    • cites [27] Norman, 2021, Post-error recruitment of frontal sensory cortical projections promotes attention in mice, Neuron source

      Not checked in the free run.

    • cites [28] Muir, 2018, In vivo fiber photometry reveals signature of future stress susceptibility in nucleus accumbens, Neuropsychopharmacology source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given
    § Behavioral assays

    Procedures were carried out in accordance with protocols approved by the Institutional Animal Care and Use Committee at the Icahn School of Medicine at Mount Sinai.

    “Procedures were carried out in accordance with protocols approved by the Institutional Animal Care and Use Committee at the Icahn School of Medicine at Mount Sinai.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data
    § Novel social interaction elicits c-fos activation in the PIL

    Mice were excluded from DREADD analyses for low viral expression of DREADDs or aggressive behavior during free social interaction in the habituation-dishabituation paradigm.

    “Mice were excluded from analyses for low viral expression of DREADDs (n = 1 male, 3 females) or aggressive behavior during free social interaction in the habituation-dishabituation paradigm (n = 3 males).”
    Quote in the paperNot a substantial claim
26 of 26

  • The paper relies on this without support.

    The specific activity and role of glutamatergic PIL neurons during social interactions had not yet been assessed.

    “Glutamatergic neurons are a major component of the PIL; however, their specific activity and role during social interactions has not yet been assessed.”

  • The paper relies on this without support.

    It remained unknown how PIL neurons respond, in real-time, to social interactions with novel same-sex or opposite-sex counterparts.

    “While together these findings suggest that the PIL may play a role in social behavior, it remains unknown how PIL neurons respond, in real-time, to social interactions with novel same-sex or oppositesex counterparts.”

  • The paper relies on this without support.

    The specific contribution of glutamatergic neurons to social behaviors had not yet been assessed.

    “Additionally, the specific contribution of glutamatergic neurons to social behaviors has not yet been assessed.”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Statistics recomputed

Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.

  • Not confirmedt(24) = 2.91reported p = .03 · recomputed p = .008

    “t(24) = 2.91, p = .03”

  • Not confirmedt(24) = 3.92reported p = .003 · recomputed p < .001

    “t(24) = 3.92, p = .003”

  • ConsistentF(1, 13) = 9.07reported p = .01 · recomputed p = .010

    “F(1,13) = 9.07, p = .01”

  • ConsistentF(1, 13) = 10.68reported p = .006 · recomputed p = .006

    “F(1, 13) = 10.68, p = .006”

  • ConsistentF(3, 24) = 3.31reported p = .037 · recomputed p = .037

    “F(3,24) = 3.31, p = .037”

  • ConsistentF(3, 24) = 3.17reported p = .043 · recomputed p = .043

    “F(3,24) = 3.17, p = .043”

6 of 6

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • c-fos ANOVA degrees of freedom do not match the stated sample size

    Minor

    Three mice per sex in each of three conditions gives 18 mice. A two-way ANOVA with sex and condition would have 12 residual degrees of freedom, not the reported 11; the reported value implies one fewer analyzed mouse than the stated sample size.

1 of 1

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Leithead, A. B., Godino, A., Barbier, M., & Harony-Nicolas, H.
Affiliations
Icahn School of Medicine at Mount Sinai (US)
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2024-01
Volume
95
Issue
2
Pages
112-122
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2023.05.016
PMC
PMC10676449
OpenAlex
W4378470429
Semantic Scholar
6cd55d9d9ecb8d9f99238f8d4cc96156bbb2d262
Cited by
21
References
51
Citations by year
2026: 3 · 2025: 7 · 2024: 9 · 2023: 2
FWCI
6.22
Type
journal article
Language
en
Open access
Licence
Locations
  • Biological Psychiatry (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Mental Health (F31MH129025)
Topics
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
thalamus, glutamatergic neurons, social interaction, social behavior, c-fos, fiber photometry, DREADD inhibition, social preferences, social investigation, sex differences
MeSH terms
Social Interaction, Animals, Female, Male, Neurons, Social Behavior, Thalamus, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review