Optogenetics publications

Background: Norepinephrine (NE) is involved in auditory fear conditioning (AFC) in posttraumatic stress disorder (PTSD). However, it is still unclear how it acts on neurons. Objective: We aimed to investigate whether the activation of the β-adrenergic receptor (β-AR) improves AFC by sensitization of the prelimbic (PL) cortex at the animal, cellular and molecular levels. Methods: In vivo single-cell electrophysiological recording was used to characterize the changes in neurons in the PL cortex after AFC. Then, PL neurons were measured under inhibition with the optogenetic method and local administration of the β-AR agonist isoprenaline (ISO) or the GABAaR agonist muscimol. Western blotting and immunohistochemistry were finally used to assess molecular changes. Results: Noise and low-frequency tones induced similar AFC. The expression of β-ARs was upregulated in the PL cortex after fear conditioning. Microinjection of muscimol into the PL cortex blocked the conformation of AFC, whereas ISO injection facilitated AFC. Moreover, PL neurons can be distinguished into two types, with type I but not type II neurons responding to conditioned sound and being regulated by β-ARs. Conclusion: Our results showed that β-ARs in the PL cortex regulate conditional fear learning by activating type I PL neurons.

Little is known about the functions of Group II metabotropic glutamate receptors (mGluRs2/3) in the inferior colliculus (IC), a midbrain structure that is a major integration region of the central auditory system. We investigated how these receptors modulate sound-evoked and spontaneous firing in the mouse IC in vivo We first performed immunostaining and tested hearing thresholds to validate vesicular GABA transporter (VGAT)-ChR2 transgenic mice on a mixed CBA/CaJ x C57BL/6J genetic background. Transgenic animals allowed for optogenetic cell-type identification. Extracellular single neuron recordings were obtained before and after pharmacological mGluR2/3 activation. We observed increased sound-evoked firing, as assessed by the rate-level functions (RLFs), in a subset of both GABAergic and non-GABAergic IC neurons following mGluR2/3 pharmacological activation. These neurons also displayed elevated spontaneous excitability and were distributed throughout the IC area tested, suggesting a widespread mGluR2/3 distribution in the mouse IC.

The ability to understand speech relies on accurate auditory processing of complex sounds. Individuals with Parkinson’s disease suffer from speech perception deficits, suggesting that dopamine is involved in the encoding of complex sounds. Recent studies have demonstrated that dopamine has heterogeneous effects on the responses of many neurons in the inferior colliculus (IC) of mice, although the strongest effect is to suppress neural activity. However, it was previously unknown which dopamine receptors are involved in modulating neuronal responses, and whether the observed preponderance of depressive effects reflects the endogenous dopamine system in the IC. In this study, we tested whether dopamine acts via D1- and/or D2-like receptors to alter responses of IC neurons in female and male mice. We also tested the effect of optogenetically induced dopamine release on auditory responses in the IC. We found that the effects of dopamine in the IC occur via D2-like receptors. In iontophoretic and freely behaving experiments, the single-unit and multi-unit effects of dopamine and a D2-like agonist were heterogeneous as both either increased or decreased responses of IC neurons to tones, while a D2-like antagonist had opposite effects. We also found that optogenetic activation of the endogenous dopamine system in the IC alters responses of auditory neurons. Similar to the effects of exogenous dopamine application, optogenetic induction of endogenous dopamine release heterogeneously altered auditory responses in the majority of cells in mice expressing channelrhodopsin-2 (ChR2). Understanding how dopamine modulates auditory processing will ultimately inform therapies targeting mechanisms underlying auditory-related communication disorders.

Plasticity of thalamocortical (TC) synapses is robust during early development and becomes limited in the adult brain. We previously reported that a short duration of deafening strengthens TC synapses in the primary visual cortex (V1) of adult mice. Here, we demonstrate that deafening restores NMDA receptor (NMDAR)-dependent long-term potentiation (LTP) of TC synapses onto principal neurons in V1 layer 4 (L4), which is accompanied by an increase in NMDAR function. In contrast, deafening did not recover long-term depression (LTD) at TC synapses. Potentiation of TC synapses by deafening is absent in parvalbumin-positive (PV+) interneurons, resulting in an increase in feedforward excitation to inhibition (E/I) ratio. Furthermore, we found that a brief duration of deafening adult mice recovers rapid ocular dominance plasticity (ODP) mainly by accelerating potentiation of the open-eye responses. Our results suggest that cross-modal sensory deprivation promotes adult cortical plasticity by specifically recovering TC-LTP and increasing the E/I ratio.

Grunts are fish that are well known to vocalize, but how they produce their grunting sounds has not been clearly identified. In addition to characterizing acoustic signals and hearing in the French grunt Haemulon flavolineatum, the present study investigates the sound-production mechanism of this species by means of high-speed X-ray videos and scanning electron microscopy of the pharyngeal jaw apparatus. Vocalizations consist of a series of stridulatory sounds: grunts lasting ~47 ms with a mean period of 155 ms and a dominant frequency of ~700 Hz. Auditory capacity was determined to range from 100 to 600 Hz, with greatest sensitivity at 300 Hz (105.0±11.8 dB re. 1 μPa). This suggests that hearing is not tuned exclusively to detect the sounds of conspecifics. High-speed X-ray videos revealed how pharyngeal jaws move during sound production. Traces of erosion on teeth in the fourth ceratobranchial arch suggest that they are also involved in sound production. The similarity of motor patterns of the upper and lower pharyngeal jaws between food processing and sound production indicates that calling is an exaptation of the food-processing mechanism.