We live in a world that is largely socially constructed, and we are constantly involved in and fundamentally influenced by a broad array of complex social interactions. Social behaviors among conspecifics, either conflictive or cooperative, are exhibited by all sexually reproducing animal species and are essential for the health, survival, and reproduction of animals. Conversely, impairment in social function is a prominent feature of several neuropsychiatric disorders, such as autism spectrum disorders and schizophrenia. Despite the importance of social behaviors, many fundamental questions remain unanswered. How is social sensory information processed and integrated in the nervous system? How are different social behavioral decisions selected and modulated in brain circuits? Here we discuss conceptual issues and recent advances in our understanding of brain regions and neural circuit mechanisms underlying the regulation of social behaviors.

HistoryA 25-year-old woman with recently diagnosed systemic lupus erythematosus and class IV lupus nephritis confirmed with biopsy and treated with mycophenolate mofetil presented with a 2-day history of progressively worsening edema of her face and lower extremities. She had no antecedent infection or vaccination. She was admitted to the hospital and treated with methylprednisolone, furosemide, and C1 esterase inhibitor. On hospital day 2, she experienced a witnessed generalized tonic-clonic seizure. At that time, she became hypoxic and was intubated for airway protection. Her laboratory study results preceding the seizure were remarkable for hyponatremia, with a blood sodium level of 122 mEq/L (122 mmol/L) (normal range, 135-145 mEq/L [134-145 mmol/L]), which was corrected to 137 mEq/L (137 mmol/L) over 48 hours. Same-day cerebrospinal fluid analysis was unremarkable, and unenhanced head CT findings (not shown) were normal, with no evidence of intracranial hemorrhage or edema.

HistoryA 25-year-old woman with recently diagnosed systemic lupus erythematosus and class IV lupus nephritis confirmed with biopsy and treated with mycophenolate mofetil presented with a 2-day history of progressively worsening edema of her face and lower extremities. She had no antecedent infection or vaccination. She was admitted to the hospital and treated with methylprednisolone, furosemide, and C1 esterase inhibitor. On hospital day 2, she experienced a witnessed generalized tonic-clonic seizure. At that time, she became hypoxic and was intubated for airway protection. Her laboratory study results preceding the seizure were remarkable for hyponatremia, with a blood sodium level of 122 mEq/L (122 mmol/L) (normal range, 135-145 mEq/L [134-145 mmol/L]), which was corrected to 137 mEq/L (137 mmol/L) over 48 hours. Same-day cerebrospinal fluid analysis was unremarkable, and unenhanced head CT findings (not shown) were normal, with no evidence of intracranial hemorrhage or edema.Her subsequent hospital course was complicated by renal failure requiring continuous renal replacement therapy, hypertension (systolic blood pressure ranging from 140 to 190 mm Hg), anemia requiring blood transfusions, thrombocytopenia, and pneumonia. She remained intubated with a limited neurologic examination due to sedative medications until hospital day 10. After extubation, she was noted to have a right gaze preference. She was able to speak in short phrases and follow simple commands. Neurologic examination was notable for drowsiness, right gaze deviation, direction-changing torsional nystagmus, horizontal ophthalmoplegia, and generalized symmetric weakness without upper motor neuron signs. The following day (hospital day 11), unenhanced MRI of the brain was performed along with MR angiography of the brain. Biopsy of the temporal artery was normal, without evidence of inflammation.

BACKGROUND: Cerebral microdialysis (CMD) is an FDA-approved multimodal invasive monitoring technique that provides local brain metabolism measurements through continuous interstitial brain fluid sampling at the bedside. The past applications in traumatic brain injury and subarachnoid hemorrhage show that acute brain injury (ABI) can lead to a metabolic crisis reflected by changes in cerebral glucose, pyruvate, and lactate. However, limited literature exists on CMD in spontaneous intracerebral hemorrhage (ICH). CASE DESCRIPTION: A 45-year-old woman presented with a Glasgow Coma Scale of 8T and left frontal ICH with a 6 mm midline shift. She underwent craniotomy and ICH evacuation. Intraoperatively, CMD, brain tissue oxygenation (PbtO2), intracranial pressure (ICP), and cerebral blood flow (CBF) catheters were placed, targeted toward the peri-hematoma region. Postoperatively, ICP was normal; however, PbtO2, CBF, glucose, and lactate/ pyruvate ratio were abnormal. Due to concern for the metabolic crisis, poor examination, and hydrocephalus on computed tomography of the head (CTH), she underwent external ventricular drainage (EVD). Post-EVD, all parameters normalized (P < 0.05 on Students t-test). Monitors were removed, and she was discharged to a nursing facility with a modified Rankin scale of 4. CONCLUSION: Here, we demonstrate the safe implementation of CMD in ICH and the use of CMD in tandem with PbtO2/ICP/CBF to guide treatment in ICH. Despite a normal ICP, numerous cerebral metabolic derangements existed and improved after cerebrospinal fluid diversion. A normal ICP may not reflect underlying metabolic-substrate demands of the brain during ABI. CMD and PbtO2/CBF monitoring augment traditional ICP monitoring in brain injury. Further prospective studies will be needed to understand further the interplay between ICP, PbtO2, CBF, and CMD values in ABI.

Behavioral, physiological, and anatomical evidence indicates that the dorsal and ventral zones of the hippocampus have distinct roles in cognition. How the unique functions of these zones might depend on differences in synaptic and neuronal function arising from the strikingly different gene expression profiles exhibited by dorsal and ventral CA1 pyramidal cells is unclear. To begin to address this question, we investigated the mechanisms underlying differences in synaptic transmission and plasticity at dorsal and ventral Schaffer collateral (SC) synapses in the mouse hippocampus. We find that, although basal synaptic transmission is similar, SC synapses in the dorsal and ventral hippocampus exhibit markedly different responses to θ frequency patterns of stimulation. In contrast to dorsal hippocampus, θ frequency stimulation fails to elicit postsynaptic complex-spike bursting and does not induce LTP at ventral SC synapses. Moreover, EPSP-spike coupling, a process that strongly influences information transfer at synapses, is weaker in ventral pyramidal cells. Our results indicate that all these differences in postsynaptic function are due to an enhanced activation of SK-type K⁺ channels that suppresses NMDAR-dependent EPSP amplification at ventral SC synapses. Consistent with this, mRNA levels for the SK3 subunit of SK channels are significantly higher in ventral CA1 pyramidal cells. Together, our findings indicate that a dorsal-ventral difference in SK channel regulation of NMDAR activation has a profound effect on the transmission, processing, and storage of information at SC synapses and thus likely contributes to the distinct roles of the dorsal and ventral hippocampus in different behaviors.SIGNIFICANCE STATEMENT Differences in short- and long-term plasticity at Schaffer collateral (SC) synapses in the dorsal and ventral hippocampus likely contribute importantly to the distinct roles of these regions in cognition and behavior. Although dorsal and ventral CA1 pyramidal cells exhibit markedly different gene expression profiles, how these differences influence plasticity at SC synapses is unclear. Here we report that increased mRNA levels for the SK3 subunit of SK-type K⁺ channels in ventral pyramidal cells is associated with an enhanced activation of SK channels that strongly suppresses NMDAR activation at ventral SC synapses. This leads to striking differences in multiple aspects of synaptic transmission at dorsal and ventral SC synapses and underlies the reduced ability of ventral SC synapses to undergo LTP.

Social behaviors, including behaviors directed toward young offspring, exhibit striking sex differences. Understanding how these sexually dimorphic behaviors are regulated at the level of circuits and transcriptomes will provide insights into neural mechanisms of sex-specific behaviors. Here, we uncover a sexually dimorphic role of the medial amygdala (MeA) in governing parental and infanticidal behaviors. Contrary to traditional views, activation of GABAergic neurons in the MeA promotes parental behavior in females, while activation of this population in males differentially promotes parental versus infanticidal behavior in an activity-level-dependent manner. Through single-cell transcriptomic analysis, we found that molecular sex differences in the MeA are specifically represented in GABAergic neurons. Collectively, these results establish crucial roles for the MeA as a key node in the neural circuitry underlying pup-directed behaviors and provide important insight into the connection between sex differences across transcriptomes, cells, and circuits in regulating sexually dimorphic behavior.

Relating genetic variants to behavior remains a fundamental challenge. To assess the utility of DNA methylation marks in discovering causative variants, we examined their relationship to genetic variation by generating single-nucleus methylomes from the hippocampus of eight inbred mouse strains. At CpG sequence densities under 40 CpG/Kb, cells compensate for loss of methylated sites by methylating additional sites to maintain methylation levels. At higher CpG sequence densities, the exact location of a methylated site becomes more important, suggesting that variants affecting methylation will have a greater effect when occurring in higher CpG densities than in lower. We found this to be true for a variant's effect on transcript abundance, indicating that candidate variants can be prioritized based on CpG sequence density. Our findings imply that DNA methylation influences the likelihood that mutations occur at specific sites in the genome, supporting the view that the distribution of mutations is not random.

The persistence of long-lasting changes in synaptic connectivity that underlie long-term memory require new RNA and protein synthesis. To elucidate the temporal pattern of gene expression that gives rise to long-lasting neuronal plasticity, we analyzed differentially-expressed (DE) RNAs in mouse hippocampal slices following induction of late phase long-term potentiation (L-LTP) specifically within pyramidal excitatory neurons using Translating Ribosome Affinity Purification RNA sequencing (TRAP-seq). We detected time-dependent changes in up- and down-regulated ribosome-associated mRNAs over 2 h following L-LTP induction, with minimal overlap of DE transcripts between time points. TRAP-seq revealed greater numbers of DE transcripts and magnitudes of LTP-induced changes than RNA-seq of all cell types in the hippocampus. Neuron-enriched transcripts had greater changes at the ribosome-loading level than the total RNA level, while RNA-seq identified many non-neuronal DE mRNAs. Our results highlight the importance of considering both time course and cell-type specificity in activity-dependent gene expression during memory formation.