Browsing by Author "Natividad, Luis A."
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- Corticotropin-Releasing Factor Receptor-1 Neurons in the Lateral Amygdala Display Selective Sensitivity to Acute and Chronic Ethanol ExposureAgoglia, Abigail E.; Zhu, ManHua; Ying, Rose; Sidhu, Harpreet; Natividad, Luis A.; Wolfe, Sarah A.; Buczynski, Matthew W.; Contet, Candice; Parsons, Loren H.; Roberto, Marisa; Herman, Melissa A. (2020-03)The lateral amygdala (LA) serves as the point of entry for sensory information within the amygdala complex, a structure that plays a critical role in emotional processes and has been implicated in alcohol use disorders. Within the amygdala, the corticotropin-releasing factor (CRF) system has been shown to mediate some of the effects of both stress and ethanol, but the effects of ethanol on specific CRF1 receptor circuits in the amygdala have not been fully established. We used male CRF1:GFP reporter mice to characterize CRF1-expressing (CRF1(+)) and nonexpressing (CRF1(-)) LA neurons and investigate the effects of acute and chronic ethanol exposure on these populations. The CRF1(+) population was found to be composed predominantly of glutamatergic projection neurons with a minority subpopulation of interneurons. CRF1(+) neurons exhibited a tonic conductance that was insensitive to acute ethanol. CRF1(-) neurons did not display a basal tonic conductance, but the application of acute ethanol induced a delta GABA(A) receptor subunit-dependent tonic conductance and enhanced phasic GABA release onto these cells. Chronic ethanol increased CRF1(+) neuronal excitability but did not significantly alter phasic or tonic GABA signaling in either CRF1(+) or CRF1(-) cells. Chronic ethanol and withdrawal also did not alter basal extracellular GABA or glutamate transmitter levels in the LA/BLA and did not alter the sensitivity of GABA or glutamate to acute ethanol-induced increases in transmitter release. Together, these results provide the first characterization of the CRF1(+) population of LA neurons and suggest mechanisms for differential acute ethanol sensitivity within this region.
- From Synapse to Function: A Perspective on the Role of Neuroproteomics in Elucidating Mechanisms of Drug AddictionNatividad, Luis A.; Buczynski, Matthew W.; McClatchy, Daniel B.; Yates, John R. (MDPI, 2018-12-09)Drug addiction is a complex disorder driven by dysregulation in molecular signaling across several different brain regions. Limited therapeutic options currently exist for treating drug addiction and related psychiatric disorders in clinical populations, largely due to our incomplete understanding of the molecular pathways that influence addiction pathology. Recent work provides strong evidence that addiction-related behaviors emerge from the convergence of many subtle changes in molecular signaling networks that include neuropeptides (neuropeptidome), protein-protein interactions (interactome) and post-translational modifications such as protein phosphorylation (phosphoproteome). Advancements in mass spectrometry methodology are well positioned to identify these novel molecular underpinnings of addiction and further translate these findings into druggable targets for therapeutic development. In this review, we provide a general perspective of the utility of novel mass spectrometry-based approaches for addressing critical questions in addiction neuroscience, highlighting recent innovative studies that exemplify how functional assessments of the neuroproteome can provide insight into the mechanisms of drug addiction.