Functional laminar architecture of rat primary auditory cortex following acoustic trauma

Exposure to loud sound can cause a series of hearing problems, the most common being tinnitus or hearing loss (temporary or permanent). Furthermore, tinnitus caused due to acoustic trauma may be observed with or without hearing loss, making it harder for tinnitus researchers to understand the pathology of this condition. Despite extensive studies in both animal and human subjects, it is still not fully understood how acoustic trauma can change neuronal activity in the auditory cortex. Several animal studies suggest changes in auditory tuning properties and increase in spontaneous activity after exposure to acoustic trauma. However, there are several discrepancies in observed changes. One possible explanation for this could be that these findings represent an average response across cortical depths which could mask the layer specific alteration in neural activity following acoustic trauma because previous studies have shown laminar specific evoked and spontaneous activity. In this study we tested the hypothesis that acoustic trauma alters neural activity in a layer-specific manner. Rats were anesthetised with urethane anaesthesia and recordings were obtained using multichannel linear silicon probes inserted vertically into the primary auditory cortex. The animals were exposed (bilaterally) to one octave white noise centred at 16 kHz, at 110 dB SPL for 1 hour. Spontaneous and auditory-evoked activity was measured before trauma and then one and two hour time-points after the acoustic trauma. We quantified laminar specific and average changes in different tuning curve parameters such as threshold, characteristic frequency, bandwidth, sparseness, spontaneous firing rate and burst like activity after trauma exposure in three different frequency regions of primary auditory cortex. We observed laminar-specific changes in auditory tuning properties such as increase in threshold and spontaneous activity mainly in layer V of the primary auditory cortex following acoustic trauma. Furthermore, we also observed increase in burst-like spiking in the superficial layers. These findings support the hypothesis that acute effects of acoustic trauma on auditory cortical population activity is laminar-specific. These findings provide essential information regarding the changes in circuit mechanisms that develop following acoustic trauma which are critical for enhancing our knowledge about the pathology of these conditions and also to identify new potential targets to treat them.Exposure to loud sound can cause a series of hearing problems, the most common being tinnitus or hearing loss (temporary or permanent). Furthermore, tinnitus caused due to acoustic trauma may be observed with or without hearing loss, making it harder for tinnitus researchers to understand the pathology of this condition. Despite extensive studies in both animal and human subjects, it is still not fully understood how acoustic trauma can change neuronal activity in the auditory cortex. Several animal studies suggest changes in auditory tuning properties and increase in spontaneous activity after exposure to acoustic trauma. However, there are several discrepancies in observed changes. One possible explanation for this could be that these findings represent an average response across cortical depths which could mask the layer specific alteration in neural activity following acoustic trauma because previous studies have shown laminar specific evoked and spontaneous activity. In this study we tested the hypothesis that acoustic trauma alters neural activity in a layer-specific manner. Rats were anesthetised with urethane anaesthesia and recordings were obtained using multichannel linear silicon probes inserted vertically into the primary auditory cortex. The animals were exposed (bilaterally) to one octave white noise centred at 16 kHz, at 110 dB SPL for 1 hour. Spontaneous and auditory-evoked activity was measured before trauma and then one and two hour time-points after the acoustic trauma. We quantified laminar specific and average changes in different tuning curve parameters such as threshold, characteristic frequency, bandwidth, sparseness, spontaneous firing rate and burst like activity after trauma exposure in three different frequency regions of primary auditory cortex. We observed laminar-specific changes in auditory tuning properties such as increase in threshold and spontaneous activity mainly in layer V of the primary auditory cortex following acoustic trauma. Furthermore, we also observed increase in burst-like spiking in the superficial layers. These findings support the hypothesis that acute effects of acoustic trauma on auditory cortical population activity is laminar-specific. These findings provide essential information regarding the changes in circuit mechanisms that develop following acoustic trauma which are critical for enhancing our knowledge about the pathology of these conditions and also to identify new potential targets to treat them

PACAP neurons in the ventromedial hypothalamic nucleus are glucose inhibited and their selective activation induces hyperglycaemia

This is the final version. Available from Frontiers Media via the DOI in this record.Background: Glucose-sensing neurons are located in several parts of the brain, but are concentrated in the ventromedial nucleus of the hypothalamus (VMH). The importance of these VMH neurons in glucose homeostasis is well-established, however, little is known about their individual identity. In the present study, we identified a distinct glucose-sensing population in the VMH and explored its place in the glucose-regulatory network. Methods: Using patch-clamp electrophysiology on Pacap-cre::EYFP cells, we explored the glucose-sensing ability of the pituitary adenylate cyclase-activating peptide (PACAP) neurons both inside and outside the VMH. We also mapped the efferent projections of these neurons using anterograde and retrograde tracing techniques. Finally, to test the functionality of PACAPVMH in vivo, we used DREADD technology and measured systemic responses. Results: We demonstrate that PACAP neurons inside (PACAPVMH), but not outside the VMH are intrinsically glucose inhibited (GI). Anatomical tracing techniques show that PACAPVMH neurons project to several areas that can influence autonomic output. In vivo, chemogenetic stimulation of these neurons inhibits insulin secretion leading to reduced glucose tolerance, implicating their role in systemic glucose regulation. Conclusion: These findings are important as they identify, for the first time, a specific VMH neuronal population involved in glucose homeostasis. Identifying the different glucose-sensing populations in the VMH will help piece together the different arms of glucose regulation providing vital information regarding central responses to glucose metabolic disorders including hypoglycaemia.Biotechnology and Biological Sciences Research Council (BBSRC)Wellcome TrustUniversity of ManchesterDiabetes UKMedical Research Counci