Biology subjects

Martinez Gonzalez, S.

Publications and source records attributed to Martinez Gonzalez, S..

3 recordsLinked to original sources

bioRxiv2023

The parabrachial to central amygdala circuit is a key mediator of injury-induced pain sensitization

The spino-ponto-amygdaloid pathway is a major ascending circuit relaying nociceptive information from the spinal cord to the brain. Potentiation of excitatory synaptic transmission in the parabrachial nucleus (PbN) to central amygdala (CeA) pathway has been reported in rodent models of persistent pain. At the behavioral level, the PbN[->]CeA pathway has been proposed to serve as a general alarm system to potential threats that modulates pain-related escape behaviors, threat memory, aversion, and affective-motivational (but not somatosensory) responses to painful stimuli. Increased sensitivity to previously innocuous somatosensory stimulation is a hallmark of chronic pain. Whether the PbN[->]CeA circuit contributes to heightened peripheral sensitivity following an injury, however, remains unknown. Here, we demonstrate that activation of CeA-projecting PbN neurons contributes to injury-induced behavioral hypersensitivity but not baseline nociception in male and female mice. Using optogenetic assisted circuit mapping, we confirmed a functional excitatory projection from PbN[->]CeA that is independent of the genetic or firing identity of CeA cells. We then showed that peripheral noxious stimulation increases the expression of the neuronal activity marker c-Fos in CeA-projecting PbN neurons and chemogenetic inactivation of these cells reduces behavioral hypersensitivity in models of neuropathic and inflammatory pain without affecting baseline nociception. Lastly, we show that chemogenetic activation of CeA-projecting PbN neurons is sufficient to induce bilateral hypersensitivity without injury. Together, our results demonstrate that the PbN[->]CeA pathway is a key modulator of pain-related behaviors that can amplify responses to somatosensory stimulation in pathological states without affecting nociception under normal physiological conditions. Significance StatementEarly studies identified the spino-ponto-amygdaloid pathway as a major ascending circuit conveying nociceptive inputs from the spinal cord to the brain. The functional significance of this circuit to injury-induced hypersensitivity, however, remains unknown. Here, we addressed this gap in knowledge using viral-mediated anatomical tracers, ex-vivo electrophysiology and chemogenetic intersectional approaches in rodent models of persistent pain. We found that activation of this pathway contributes to injury-induced hypersensitivity, directly demonstrating a critical function of the PbN[->]CeA circuit in pain modulation.

neuroscience↗

bioRxiv2022

Sex differences in pain-related behaviors and clinical progression of disease in mouse models of visceral pain

Previous studies have reported sex differences in irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) patients, including differences in visceral pain perception. Despite this, sex differences in behavioral manifestations of visceral pain and underlying pathology of the gastrointestinal tract have been largely understudied in preclinical research. In this study, we evaluated potential sex differences in spontaneous visceral nociceptive responses, referred abdominal hypersensitivity, disease progression and bowel pathology in mouse models of acute and persistent colon inflammation. Our experiments show that females exhibit more visceral nociceptive responses and referred abdominal hypersensitivity than males in the context of acute but not persistent colon inflammation. We further demonstrate that, following acute and persistent colon inflammation, visceral pain-related behavioral responses in females and males are distinct, with increases in licking of the abdomen only observed in females and increases in abdominal contractions only seen in males. During persistent colon inflammation, males exhibit worse disease progression than females, which is manifested as worse physical appearance and higher weight loss. However, no measurable sex differences were observed in persistent inflammation-induced bowel pathology, stool consistency or fecal blood. Overall, our findings demonstrate that visceral pain-related behaviors and disease progression in the context of acute and persistent colon inflammation are sex-dependent, highlighting the importance of considering sex as a biological variable in future mechanistic studies of visceral pain as well as in the development of diagnostics and therapeutic options for chronic gastrointestinal diseases.

neuroscience↗

bioRxiv2019

Cell-type specificity of neuronal excitability and morphology in the central amygdala

Central amygdala (CeA) neurons expressing protein kinase C delta (PKC{delta}+) 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 PKC{delta}+ CeLC neurons. Som+ neurons, for example, are more excitable, compact and with more complex dendritic arborizations than PKC{delta}+ neurons. Cell size, intrinsic membrane properties, and anatomical 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 PKC{delta}+ 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 PKC{delta}+ and Som+ cells that support cell-type-specific function in the CeA.

neuroscience↗