Yarimar Carrasquillo, Ph.D.

@article{pmid33188006,

title = {Cell-Type Specificity of Neuronal Excitability and Morphology in the Central Amygdala},

author = {Anisha P Adke and Aleisha Khan and Hye-Sook Ahn and Jordan J Becker and Torri D Wilson and Spring Valdivia and Yae K Sugimura and Santiago Martinez Gonzalez and Yarimar Carrasquillo},

url = {https://pubmed.ncbi.nlm.nih.gov/33188006/},

doi = {10.1523/ENEURO.0402-20.2020},

issn = {2373-2822},

year  = {2019},

date = {2019-10-08},

journal = {eNeuro},

volume = {8},

number = {1},

abstract = {Central amygdala (CeA) neurons expressing protein kinase Cδ (PKCδ) or somatostatin (Som) differentially modulate diverse behaviors. The underlying features supporting cell-type-specific function in the CeA, however, remain unknown. Using whole-cell patch-clamp electrophysiology in acute mouse brain slices and biocytin-based neuronal reconstructions, we demonstrate that neuronal morphology and relative excitability are two distinguishing features between Som and PKCδ neurons in the laterocapsular subdivision of the CeA (CeLC). Som neurons, for example, are more excitable, compact, and with more complex dendritic arborizations than PKCδ neurons. Cell size, intrinsic membrane properties, and anatomic localization were further shown to correlate with cell-type-specific differences in excitability. Lastly, in the context of neuropathic pain, we show a shift in the excitability equilibrium between PKCδ and Som neurons, suggesting that imbalances in the relative output of these cells underlie maladaptive changes in behaviors. Together, our results identify fundamentally important distinguishing features of PKCδ and Som cells that support cell-type-specific function in the CeA.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31597095,

title = {Dual and Opposing Functions of the Central Amygdala in the Modulation of Pain},

author = {Torri D Wilson and Spring Valdivia and Aleisha Khan and Hye-Sook Ahn and Anisha P Adke and Santiago Martinez Gonzalez and Yae K Sugimura and Yarimar Carrasquillo},

url = {https://pubmed.ncbi.nlm.nih.gov/31597095/},

doi = {10.1016/j.celrep.2019.09.011},

issn = {2211-1247},

year  = {2019},

date = {2019-10-01},

urldate = {2019-10-01},

journal = {Cell Rep},

volume = {29},

number = {2},

pages = {332--346.e5},

abstract = {Pain perception is essential for survival and can be amplified or suppressed by expectations, experiences, and context. The neural mechanisms underlying bidirectional modulation of pain remain largely unknown. Here, we demonstrate that the central nucleus of the amygdala (CeA) functions as a pain rheostat, decreasing or increasing pain-related behaviors in mice. This dual and opposing function of the CeA is encoded by opposing changes in the excitability of two distinct subpopulations of GABAergic neurons that receive excitatory inputs from the parabrachial nucleus (PB). Thus, cells expressing protein kinase C-delta (CeA-PKCδ) are sensitized by nerve injury and increase pain-related responses. In contrast, cells expressing somatostatin (CeA-Som) are inhibited by nerve injury and their activity drives antinociception. Together, these results demonstrate that the CeA can amplify or suppress pain in a cell-type-specific manner, uncovering a previously unknown mechanism underlying bidirectional control of pain in the brain.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid22615428,

title = {A-type K+ channels encoded by Kv4.2, Kv4.3 and Kv1.4 differentially regulate intrinsic excitability of cortical pyramidal neurons},

author = {Yarimar Carrasquillo and Andreas Burkhalter and Jeanne M Nerbonne},

url = {https://pubmed.ncbi.nlm.nih.gov/22615428/},

doi = {10.1113/jphysiol.2012.229013},

issn = {1469-7793},

year  = {2012},

date = {2012-08-01},

urldate = {2012-08-01},

journal = {J Physiol},

volume = {590},

number = {16},

pages = {3877--3890},

abstract = {Rapidly activating and rapidly inactivating voltage-gated A-type K+ currents, IA, are key determinants of neuronal excitability and several studies suggest a critical role for the Kv4.2 pore-forming α subunit in the generation of IA channels in hippocampal and cortical pyramidal neurons. The experiments here demonstrate that Kv4.2, Kv4.3 and Kv1.4 all contribute to the generation of IA channels in mature cortical pyramidal (CP) neurons and that Kv4.2-, Kv4.3- and Kv1.4-encoded IA channels play distinct roles in regulating the intrinsic excitability and the firing properties of mature CP neurons. In vivo loss of Kv4.2, for example, alters the input resistances, current thresholds for action potential generation and action potential repolarization of mature CP neurons. Elimination of Kv4.3 also prolongs action potential duration, whereas the input resistances and the current thresholds for action potential generation in Kv4.3−/− and WT CP neurons are indistinguishable. In addition, although increased repetitive firing was observed in both Kv4.2−/− and Kv4.3−/− CP neurons, the increases in Kv4.2−/− CP neurons were observed in response to small, but not large, amplitude depolarizing current injections, whereas firing rates were higher in Kv4.3−/− CP neurons only with large amplitude current injections. In vivo loss of Kv1.4, in contrast, had minimal effects on the intrinsic excitability and the firing properties of mature CP neurons. Comparison of the effects of pharmacological blockade of Kv4-encoded currents in Kv1.4−/− and WT CP neurons, however, revealed that Kv1.4-encoded IA channels do contribute to controlling resting membrane potentials, the regulation of current thresholds for action potential generation and repetitive firing rates in mature CP neurons.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid18573207,

title = {Hemispheric lateralization of a molecular signal for pain modulation in the amygdala},

author = {Yarimar Carrasquillo and Robert W Gereau},

url = {https://pubmed.ncbi.nlm.nih.gov/18573207/},

doi = {10.1186/1744-8069-4-24},

issn = {1744-8069},

year  = {2008},

date = {2008-06-01},

urldate = {2008-06-01},

journal = {Mol Pain},

volume = {4},

pages = {24},

abstract = {The extracellular signal-regulated kinase (ERK) cascade has been shown to be a key modulator of pain processing in the central nucleus of the amygdala (CeA) in mice. ERK is activated in the CeA during persistent inflammatory pain and this activation is both necessary and sufficient to induce peripheral tactile hypersensitivity. Interestingly, biochemical studies show that inflammation-induced ERK activation in the CeA only occurs in the right, but not the left hemisphere. This inflammation-induced ERK activation in the right CeA is independent of the side of peripheral inflammation, suggesting that there is a dominant role of the right hemisphere in the modulation of pain by ERK activation in the CeA. However, the functional significance of this biochemical lateralization has yet to be determined. In the present study, we tested the hypothesis that modulation of pain by ERK signaling in the CeA is functionally lateralized. We acutely blocked ERK activation in the CeA by infusing the MEK inhibitor U0126 into the right or the left hemisphere and then measured the behavioral effects on inflammation-induced mechanical hypersensitivity in mice. Our results show that blockade of ERK activation in the right, but not the left CeA, decreases inflammation-induced peripheral hypersensitivity independent of the side of peripheral injury. These findings demonstrate that modulation of pain by ERK signaling in the CeA is functionally lateralized to the right hemisphere, suggesting a dominant role of the right amygdala in pain processing.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid17301163,

title = {Activation of the extracellular signal-regulated kinase in the amygdala modulates pain perception},

author = {Yarimar Carrasquillo and Robert W Gereau},

url = {https://pubmed.ncbi.nlm.nih.gov/17301163/},

doi = {10.1523/JNEUROSCI.3536-06.2007},

issn = {1529-2401},

year  = {2007},

date = {2007-02-01},

urldate = {2007-02-01},

journal = {J Neurosci},

volume = {27},

number = {7},

pages = {1543--1551},

abstract = {The amygdala has been proposed to serve as a neural center for the modulation of pain perception. Numerous anatomical and behavioral studies demonstrate that exogenous manipulations of the amygdala (i.e., lesions, drug infusions) modulate behavioral responses to acute noxious stimuli; however, little is known about the endogenous molecular changes in the amygdala that contribute to alterations in nociceptive processing during persistent noxious stimuli that resemble pathological pain conditions. In the present study, we demonstrate that endogenous molecular changes in the amygdala play a crucial role in modulating long-lasting peripheral hypersensitivity associated with persistent inflammation and we further identify the extracellular signal-regulated kinase (ERK) as a molecular substrate underlying this behavioral sensitization. Using the formalin test as a mouse model of persistent inflammatory pain, we show that activation of ERK in the amygdala is both necessary for and sufficient to induce long-lasting peripheral hypersensitivity to tactile stimulation. Thus, blockade of inflammation-induced ERK activation in the amygdala significantly reduced long-lasting peripheral hypersensitivity associated with persistent inflammation, and pharmacological activation of ERK in the amygdala induced peripheral hypersensitivity in the absence of inflammation. Importantly, blockade of ERK activation in the amygdala did not affect responses to acute noxious stimuli in the absence of inflammation, indicating that modulation of nociceptive responses by amygdala ERK activation is specific to the persistent inflammatory state. Altogether, our results demonstrate a functional role of the ERK signaling cascade in the amygdala in inflammation-induced peripheral hypersensitivity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}