Following the development of magnetic resonance imaging (MRI) methods to assay the integrity of catecholamine nuclei, including the locus coeruleus (LC), there has been an effort to develop automated methods that can accurately segment this small structure in an automated manner to promote its widespread use and overcome limitations of manual segmentation. Here we characterize an automated LC segmentation approach (referred to as the funnel‐tip [FT] method) in healthy individuals and individuals with LC degeneration in the context of Alzheimer's disease (AD, confirmed with tau‐PET imaging using [18F]MK6240). The first sample included n = 190 individuals across the AD spectrum from cognitively normal to moderate AD. LC signal assayed with FT segmentation showed excellent agreement with manual segmentation (intraclass correlation coefficient [ICC] = 0.91). Compared to other methods, the FT method showed numerically higher correlation to AD status (defined by presence of tau: Cohen's d = 0.64) and AD severity (Braak stage: Pearson R = −.35, cognitive function: R = .25). In a separate sample of n = 12 control participants, the FT method showed excellent scan–rescan reliability (ICC = 0.82). In another sample of n = 30 control participants, we found that the structure of the LC defined by FT segmentation approximated its expected shape as a contiguous line: <5% of LC voxels strayed >1 voxel (0.69 mm) from this line. The FT LC segmentation shows high agreement with manual segmentation and captures LC degeneration in AD. This practical method may facilitate larger research studies of the human LC‐norepinephrine system and has potential to support future use of neuromelanin‐sensitive MRI as a clinical biomarker.
Habituation is the diminishing of a physiological response to a frequently repeated stimulus. In Aplysia, habituation to touch is mediated by the depression of the response to sensory neuron firing mediated by a decrease in transmitter release even after modest rates of action potential firing. This depression is not common among Aplysia synaptic connections suggesting the presence of a release apparatus specialized for this depression. This depression can be reversed through activation of protein kinase C and this is thought to underlie the behavior of dishabituation. We have previously noted that the calcium channel required for release, ApCaV2, has many splice isoforms in Aplysia. We found that specific splice forms of ApCaV2 and splice forms for interacting partners of ApCaV2 are preferentially used in sensory neurons, consistent with a specialized release apparatus. However, we were not able to find a specific splice uniquely required for synaptic depression. The C-terminus of ApCaV2 alpha1 subunit retains conserved binding sites for Aplysia rab-3 interacting molecule (ApRIM) and ApRIM-binding protein (ApRBP) and the C-terminus is required for full synaptic expression of ApCaV2.
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