Amygdala Intercalated Cells: Gate Keepers and Conveyors of Internal State to the Circuits of Emotion.

Generating adaptive behavioral responses to emotionally salient stimuli requires evaluation of complex associations between multiple sensations, the surrounding context, and current internal state. Neural circuits within the amygdala parse this emotional information, undergo synaptic plasticity to reflect learned associations, and evoke appropriate responses through their projections to the brain regions orchestrating these behaviors. Information flow within the amygdala is regulated by the intercalated cells (ITCs), which are densely packed clusters of GABAergic neurons that encircle the basolateral amygdala (BLA) and provide contextually relevant feedforward inhibition of amygdala nuclei, including the central and BLA. Emerging studies have begun to delineate the unique contribution of each ITC cluster and establish ITCs as key loci of plasticity in emotional learning. In this review, we summarize the known connectivity and function of individual ITC clusters and explore how different neuromodulators conveying internal state act via ITC gates to shape emotionally motivated behavior. We propose that the behavioral state-dependent function of ITCs, their unique genetic profile, and rich expression of neuromodulator receptors make them potential therapeutic targets for disorders, such as anxiety, schizophrenia spectrum, and addiction.

Deletion of ErbB4 Disrupts Synaptic Transmission and Long-Term Potentiation of Thalamic Input to Amygdalar Medial Paracapsular Intercalated Cells.

Identification of candidate risk genes and alteration in the expression of proteins involved in regulating inhibitory neuron function in various psychiatric disorders, support the notion that GABAergic neuron dysfunction plays an important role in disease etiology. Genetic variations in neuregulin and its receptor kinase ErbB4, expressed exclusively by GABAergic neurons in the CNS, have been linked with schizophrenia. In the amygdala, ErbB4 is highly expressed in GABAergic intercalated cell clusters (ITCs), which play a critical role in amygdala-dependent behaviors. It is however unknown whether ErbB4 deletion from ITCs affects their synaptic properties and function in amygdala circuitry. Here, we examined the impact of ErbB4 deletion on inhibitory and excitatory circuits recruiting medial paracapsular ITCs (mpITCs) using electrophysiological techniques. Ablation of ErbB4 in mpITCs suppressed NMDA receptor-mediated synaptic transmission at thalamo-mpITC synapses and enhanced thalamic driven GABAergic transmission onto mpITCs. Furthermore, long-term potentiation (LTP) at thalamo-mpITC synapses was compromised in ErbB4 mutant mice, indicating that ErbB4 activity is critical for LTP at these synapses. Together, our findings suggest that ErbB4 deletion from mpITCs disrupts excitation-inhibition balance and learning mechanisms in amygdala circuits.

Apical intercalated cell cluster: A distinct sensory regulator in the amygdala.

GABAergic neurons regulate different aspects of information processing in the amygdala. Among these are clusters of intercalated cells (ITCs), which have been implicated in fear-related behaviors. Although a few of the ITC clusters have been studied, the functional role of apical ITCs (apITCs) is unknown. Here, we combine monosynaptic rabies tracing with optogenetics and demonstrate that apITCs receive synaptic input from medial geniculate nucleus (MGm), posterior intralaminar nucleus (PIN), and medial dorsal nucleus of the thalamus and from a diverse range of cortical areas including temporal association, entorhinal, insular, piriform, and somatosensory cortex. Upon fear learning, PIN/MGm inputs are strengthened, indicative of their involvement in fear behaviors. 3-D reconstruction of apITCs reveals local arborization and innervation of the dorsal striatum and lateral amygdala. We further show that apITCs provide sensory feedforward inhibition to LA principal cells, a putative mechanism for controlling plasticity during fear learning.

Cerebrovascular Accident in a 65-Year-Old Patient with Rothia dentocariosa-Associated Endocarditis.

A 65-year-old male patient with a history of heart valve replacement surgery after aortic valve stenosis and a family history of heart disease presented to the emergency room with complaints of headache, fever, back pain, and general malaise. Multiple blood samples during the patient's hospitalization cultured showed Rothia dentocariosa. The patient was started on daily intravenous ceftriaxone and vancomycin. In the following weeks, the patient's condition deteriorated with additional symptoms, persistent inflammatory markers, and elevated fever consistent with R. dentocariosa infection. The patient's clinical progression led to a cerebrovascular accident that was resolved with thrombectomy. Full symptomatic relief occurred after a valve replacement. R. dentocariosa, a common mouth flora, is not commonly pathogenic. This case is of particular importance as severe complications involving this bacterium are rare. There is an extreme paucity of cases involving deadly complications of R. dentocariosa, and there is no general consensus involving standard treatment regimen for this bacterium. We believe that this paper adds to clinical knowledge surrounding R. dentocariosa.

Quality of Life Outcomes After Transcatheter Aortic Valve Replacement in Nonagenarians.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS) is an increasingly prevalent treatment in patients who are intermediate or high risk for surgical intervention. In nonagenarian patients undergoing TAVR, symptomatic relief and quality of life (QoL) outcomes have not been well established. This study explores these outcomes in this patient population that has been underrepresented in landmark clinical trials. METHODS: All patients who underwent TAVR between January 1, 2015 and December 31, 2018 at Delray Medical Center were included. The 12-item Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) score was used to assess QoL prior to and 30 days following TAVR in two patient groups: the nonagenarian group (patients ≥90 years old) and the younger group (patients <90 years old). KCCQ-OS scores were compared between these two groups. Frailty assessment included grip strength, gait speed, and activities of daily living. Unadjusted and adjusted analyses (baseline KCCQ-OS score, frailty, and Society of Thoracic Surgery perioperative risk of mortality [STS-PROM] score) were performed to assess the impact of age on QoL outcomes in both groups. RESULTS: Of the total 223 patients included in this study, a total of 46 (20.6%) were nonagenarians and 118 (52.7%) were men. KCCQ-OS scores were lower at baseline and 30-day follow-up in nonagenarians compared with the younger group (P=.70). Age was a significant predictor of 30- day KCCQ-OS in unadjusted and adjusted analyses (adjusted for baseline KCCQ-OS, frailty, and STS-PROM score). Nonagenarians had an average 6.45 points lower 30-day KCCQ-OS scores than the younger patients in adjusted analysis. However, there was a significant clinical improvement in the 30-day KCCQ-OS score in both groups (P<.001). CONCLUSIONS: Our data suggest that with appropriate patient selection, a significant clinical improvement may be expected with TAVR in nonagenarians.