LFP publications

Intracortical, horizontal connections seem ideally suited to contribute to cortical processing by spreading information across cortical space and coordinating activity between distant cortical sites. In sensory systems experiments have implicated horizontal connections in the generation of receptive fields and have in turn led to computational models of receptive field generation that rely on the contribution of horizontal connections. Testing the contribution of horizontal connections at the mesoscopic level has been difficult due to the lack of a suitable method to observe the activity of intracortical horizontal connections. Here, we develop such a method based on the analysis of the relative residues of the cortical laminar current source density reconstructions. In the auditory cortex of Mongolian gerbils, the method is then tested by manipulating the contribution of horizontal connections by surgical dissection. Our results indicate that intracortical horizontal connections contribute to the frequency-tuning of mesoscopic cortical patches. Futhermore, we dissociated a type of cortical gamma oscillation based on horizontal connections between mesoscopic patches from gamma oscillations locally generated within mesoscopic patches. The data further imply that global and local coordination of activity during sensory stimulation occur in a low and high gamma frequency band, respectively. Taken together the present data demonstrate that intracortical horizontal connections play an important role in generating cortical feature tuning and coordinate neuronal oscillations across cortex.

Hair cells detect sound, head position or water movements when their mechanosensory hair bundle is deflected. Each hair bundle has an asymmetric architecture that restricts stimulus detection to a single axis. Coordinated hair cell orientations within sensory epithelia further tune stimulus detection at the organ level. Here, we identify GPR156, an orphan GPCR of unknown function, as a critical regulator of hair cell orientation. We demonstrate that the transcription factor EMX2 polarizes GPR156 distribution, enabling it to signal through Gαi and trigger a 180° reversal in hair cell orientation. GPR156-Gαi mediated reversal is essential to establish hair cells with mirror-image orientations in mouse otolith organs in the vestibular system and in zebrafish lateral line. Remarkably, GPR156-Gαi also instructs hair cell reversal in the auditory epithelium, despite a lack of mirror-image organization. Overall, our work demonstrates that conserved GPR156-Gαi signaling is integral to the framework that builds directional responses into mechanosensory epithelia.

Animal models have demonstrated that tinnitus is a pathology of dysfunctional excitability in the central auditory system, in particular in the dorsal cochlear nucleus (DCN) of the brainstem. We used a murine model and studied whether acoustic over-exposure leading to hearing loss and tinnitus, affects long-term potentiation (LTP) at DCN multisensory synapses. Whole cell and field potential recordings were used to study the effects on release probability and synaptic plasticity, respectively in brainstem slices. Shifts in hearing threshold were quantified by auditory brainstem recordings, and gap-induced prepulse inhibition of the acoustic startle reflex was used as an index for tinnitus. An increased release probability that saturated LTP and thereby induced metaplasticity at DCN multisensory synapses, was observed 4-5days following acoustic over-exposure. Perfusion of an NMDA receptor antagonist or decreasing extracellular calcium concentration, decreased the release probability and restored LTP following acoustic over-exposure. In vivo administration of magnesium-threonate following acoustic over-exposure restored LTP at DCN multisensory synapses, and reduced gap detection deficits observed four months following acoustic over-exposure. These observations suggest that consequences of noise-induced metaplasticity could underlie the gap detection deficits that follow acoustic over-exposure, and that early therapeutic intervention could target metaplasticity and alleviate tinnitus.