Seminars

Throughout life, we are constantly exposed to a flood of sensory information, but only a small fraction reaches conscious perception and guides behavior. For example, repeated exposure to the same sound can reduce its salience through habituation, whereas associative learning between sounds and positive or negative values can enhance perception. In this seminar, I will discuss our recent and ongoing work on cortical circuit mechanisms that bidirectionally regulate auditory perception through
pathways extending beyond the auditory cortex. First, I will present our recent work on experience-dependent habituation in the mouse primary auditory cortex (A1). Using chronic two-photon calcium imaging across days, we found that repeated sound exposure reduced A1 sound responses. This neural
habituation was reversed by inactivation of the orbitofrontal cortex (OFC). Moreover, top-down projections from the OFC, but not other frontal areas, grew with daily sound experience and suppressed A1 activity through somatostatin-expressing inhibitory neurons. These results are consistent with a model in which prediction signals are formed in the OFC and cancel out anticipated sounds by generating their “negative images” in sensory cortices. I will also introduce ongoing work on an alternative sound-processing pathway through the insular cortex. The insula is a key site for integrating external sensory inputs with internal state, yet the circuit organization and behavioral role of its sound-responsive subdomain, the insular auditory field (IAF), remain poorly understood. We found that the IAF exhibits a connectivity pattern distinct from neighboring insular and auditory cortical areas. Selective silencing of the IAF impaired sound-guided reward behavior as strongly as silencing the entire auditory cortex, without affecting general reward consumption. These results raise the possibility that the auditory cortex and IAF form complementary pathways for processing sound: one extracts acoustic features, whereas the other links sound to internal state and motivated behavior.

Chronic neuropathic orofacial pain (CNOP) can be produced by surgical interventions, and it is detrimental for the quality of life of who suffer from it. The development of an experimental model similar to its clinical features is necessary for a precise approach to the study of its neurobiological basis. We propose the mental nerve compression injury as a useful model for studying different phenomena that occur in the development of such disease, from behavior for identifying phenotypes, to analyze facial expression, as well as to assess the neural substrates involved. Wild-type (WT) mice went through mental nerve compression injury to induce CNOP, and were assessed with von Frey test, for nociceptive threshold on day 3 to week 14. To determine the role of nucleus accumbens (NAc) dopamine-receptor-expressing neurons (DRn), D1- and D2R-Cre mice were infected with a genetically engineered caspase in NAc, causing specific ablation of such neurons. Mechanical sensitivity was tested before and after it, and after nerve injury. For facial expression analysis, WT mice were face-recorded in a head-fixed system during the onset of mechanical stimulation, at -1, 4 and 7 days after nerve injury; electrophysiological recordings were performed in anterior cingulate cortex (ACC). In vglut2-ires-cre mice ACC neurons were ablated in a Caspase-dependent manner. Videos were analyzed with an artificial-vision tool; firing rate z-score was calculated and analyzed with a Generalized Lineal Model to identify neurons modulated by the pain facial response. We found that injured WT mice showed mechanical hypersensitivity during the first weeks. Mice were classified in high and low threshold (HT and LT), being most of them HT mice. Most HT mice recovered from mechanical hypersensitivity, whereas most LT mice remained hypersensitive. NAc DRn ablation decreased the percentage of HT mice and increased the time of hypersensitivity recovery, suggesting this population participates in nociceptive threshold profiles and recovery capacity. The painful facial response is dependent on the stimuli force and it is exacerbated by the mental nerve lesion. GLM analysis detected a neural population modulated by the pain facial response for both stimuli, that increased its firing rate after the stimuli onset. ACC neural ablation showed no effect on the baseline facial response but abolished the changes observed in the context of neuropathic pain. This way, we found that mental nerve compression injury produces two chronic pain development phenotypes, is functional for the analysis of facial expression through artificial vision tools, and for the assessment of the neural structures involved.