The homeostatic modulation of neurotransmitter release, termed presynaptic homeostatic potentiation (PHP), is a fundamental type of neuromodulation, conserved from Drosophila to human, that stabilizes information transfer at synaptic connections throughout the nervous system. Here we demonstrate that α2δ-3, an auxiliary subunit of the presynaptic calcium channel, is required for PHP. The α2δ gene family has been linked to chronic pain, epilepsy, autism and the action of two psychiatric drugs, gabapentin and pregabalin. We demonstrate that loss of α2δ-3 blocks both the rapid induction and sustained expression of PHP due to a failure to potentiate presynaptic calcium influx and the RIM-dependent readily-releasable vesicle pool. These deficits are independent of α2δ-3-mediated regulation of baseline calcium influx and presynaptic action potential waveform. α2δ proteins reside at the extracellular face of presynaptic release sites throughout the nervous system, an ideal site to mediate rapid, trans-synaptic homeostatic signaling in health and disease.
Firing rate homeostasis (FRH) stabilizes neural activity. A pervasive and intuitive theory argues that a single variable, calcium, is detected and stabilized through regulatory feedback. A prediction is that ion channel gene mutations with equivalent effects on neuronal excitability should invoke the same homeostatic response. In agreement, we demonstrate robust FRH following either elimination of Kv4/Shal protein or elimination of the Kv4/Shal conductance. However, the underlying homeostatic signaling mechanisms are distinct. Eliminating Shal protein invokes Krüppel-dependent rebalancing of ion channel gene expression including enhanced slo, Shab, and Shaker. By contrast, expression of these genes remains unchanged in animals harboring a CRISPR-engineered, Shal pore-blocking mutation where compensation is achieved by enhanced IKDR. These different homeostatic processes have distinct effects on homeostatic synaptic plasticity and animal behavior. We propose that FRH includes mechanisms of proteostatic feedback that act in parallel with activity-driven feedback, with implications for the pathophysiology of human channelopathies.
AAPA 2022 POSTER SESSION ABSTRACTS PURPOSEPrevious studies have indicated that under-or uninsured women, such as many patients at South Main Clinic (SMC), are more likely to be diagnosed with breast cancer at later stages, impairing their quality of life and survival. To improve mammogram screening rates in the uninsured and underinsured population of South Salt Lake, the Utah Cancer Control Program partnered with SMC to provide lifesaving cancer screenings through a direct referral process. This area was considered a high priority because of its extremely low rates of cancer screening, high rates of uninsured patients, and high rates of poverty . METHODSThis retrospective study used data gathered between November 2018 and January 2021. Institutional review board approval was obtained from the University of Utah.The study subjects were patients ages 40 to 74 years who were referred between November 2018 and January 2021. Patients who refused mammogram screening services before referral were not included in this study.Data were gathered from the electronic health record and included sex, age, insurance status, mammogram order
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