RESUMEN
ABSTRACT: The thermal grill illusion (TGI), a phenomenon in which the juxtaposition of innocuous warm and cold temperatures on the skin elicits a burning sensation, offers a unique perspective to how pain occurs in response to harmless stimuli. We investigated the role of the spinal cord in the generation of the TGI across 2 experiments (total n = 80). We applied heat and cold stimuli to dermatomes, areas of skin innervated by a single spinal nerve, that mapped onto adjacent or nonadjacent spinal segments. Enhanced warm and burning ratings during the TGI were observed when cold and warm stimuli were confined within the same dermatome. Furthermore, we found the spatial organisation of warm and cold stimuli within and across dermatomes affected TGI perception. Perceived warmth and burning intensity increased when the cold stimulus projected to the segment more caudal to the warm stimulus, whereas perceived cold during the TGI decreased compared with the opposite spatial arrangement. This suggests that the perception of TGI is enhanced when cold afferents are projected to spinal segments positioned caudally in relation to those receiving warm afferents. Our results indicate distinct interaction of sensory pathways based on the segmental arrangement of afferent fibres and are consistent with current interpretations of the spread and integration of thermosensory information along the spinal cord.
Asunto(s)
Frío , Calor , Ilusiones , Médula Espinal , Sensación Térmica , Humanos , Ilusiones/fisiología , Masculino , Femenino , Sensación Térmica/fisiología , Adulto , Calor/efectos adversos , Médula Espinal/fisiología , Adulto Joven , Piel/inervación , Dolor/fisiopatología , Dimensión del Dolor/métodos , Percepción del Dolor/fisiologíaRESUMEN
Loss of connectivity between spinal V1 inhibitory interneurons and motor neurons is found early in disease in the SOD1G93A mice. Such changes in premotor inputs can contribute to homeostatic imbalance of motor neurons. Here, we show that the Extended Synaptotagmin 1 (Esyt1) presynaptic organizer is downregulated in V1 interneurons. V1 restricted overexpression of Esyt1 rescues inhibitory synapses, increases motor neuron survival, and ameliorates motor phenotypes. Two gene therapy approaches overexpressing ESYT1 were investigated; one for local intraspinal delivery, and the other for systemic administration using an AAV-PHP.eB vector delivered intravenously. Improvement of motor functions is observed in both approaches, however systemic administration appears to significantly reduce onset of motor impairment in the SOD1G93A mice in absence of side effects. Altogether, we show that stabilization of V1 synapses by ESYT1 overexpression has the potential to improve motor functions in ALS, demonstrating that interneurons can be a target to attenuate ALS symptoms.
Asunto(s)
Esclerosis Amiotrófica Lateral , Modelos Animales de Enfermedad , Interneuronas , Ratones Transgénicos , Neuronas Motoras , Sinapsis , Animales , Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/fisiopatología , Esclerosis Amiotrófica Lateral/metabolismo , Esclerosis Amiotrófica Lateral/terapia , Interneuronas/metabolismo , Neuronas Motoras/metabolismo , Ratones , Sinapsis/metabolismo , Fenotipo , Masculino , Terapia Genética/métodos , Humanos , Femenino , Superóxido Dismutasa-1/genética , Superóxido Dismutasa-1/metabolismoRESUMEN
Interoception - the physiological sense of our inner bodies - has risen to the forefront of psychological and psychiatric research. Much of this research utilizes tasks that attempt to measure the ability to accurately detect cardiac signals. Unfortunately, these approaches are confounded by well-known issues limiting their validity and interpretation. At the core of this controversy is the role of subjective beliefs about the heart rate in confounding measures of interoceptive accuracy. Here, we recast these beliefs as an important part of the causal machinery of interoception, and offer a novel psychophysical "heart rate discrimination" method to estimate their accuracy and precision. By applying this task in 223 healthy participants, we demonstrate that cardiac interoceptive beliefs are more biased, less precise, and are associated with poorer metacognitive insight relative to an exteroceptive control condition. Our task, provided as an open-source python package, offers a robust approach to quantifying cardiac beliefs.