Spontaneous activity in the developing gerbil auditory cortex in vivo involves GABAergic transmission

Abstract

A salient feature of the developing brain is that spontaneous oscillations (SOs) and waves may influence the emergence of synaptic connections. Whilst gamma-amino butyric acid (GABA) produces depolarization and may support SOs in the neurons of developing rodents, it elicits hyperpolarization and diminishes SOs in developing gerbil auditory cortex (ACx). Therefore, we asked whether SOs exist in developing gerbil ACx in vivo and if GABAergic involvement can be manipulated. In vivo extracellular recordings in P3-5 ACx revealed SOs with longer burst durations and shorter inter-event intervals compared to ACx SOs in slices. ACx was then validated by gross anatomical features and lesions created at the in vivo recording site that corresponded with the electrophysiological coordinates of thalamorecipient ACx in slices. Further, NeuroVue Red, a lipophilic dye loaded at the in vivo recording sites, stained anatomically identifiable fiber tracks between the ACx and the auditory thalamus, medial geniculate body (MG). Separately, to chronically perturb GABAergic role in SOs, P2-5 pups were administered daily with GABAA receptor blocker, bicuculline (BIC). We then recorded from P14-17 ACx neurons in slices generated after hearing onset. ACx neurons from BIC-administered pups exhibited spontaneous action potentials in contrast to subthreshold synaptic potentials in neurons from sham-injected animals. Finally, to elucidate whether the gap junction blocker mefloquine (MFQ) previously shown to dampen ACx SOs in slices affected GABAergic transmission, MFQ was acutely applied in P3-5 slices while spontaneous inhibitory postsynaptic currents (sIPSCs) were recorded. Whereas MFQ increased the amplitude and frequency of sIPSCs in ACx neurons, the broad-spectrum gap junction blocker carbenoxolone decreased sIPSC amplitudes only. Together, we show that P2-5 gerbil ACx can endogenously generate SOs in vivo. Persistence of activity in ACx in P14-17 slices from pups administered with BIC at P2-5 implies that inhibitory GABAergic activity linked with gap-junction participates in the maturation of ACx.

Plasticity of neonatal neuronal networks in very premature infants: Source localization of temporal theta activity, the first endogenous neural biomarker, in temporoparietal areas

“…These spontaneous activities appear to be genetically encoded and participate in implementation of the final functional organization of the cochlea [Kilb et al, 2011;Tritsch and Bergles, 2010;Tritsch et al, 2007]. Endogenous oscillations and waves have been reported in the thalamorecipient auditory cortex in immature animals, with an incidence of 0.4-5 waves/min, and a mean instantaneous firing of 6.4 6 1.3 Hz similar to that observed for TTA-SW in this study [Kotak et al, 2007[Kotak et al, , 2012. Endogenous oscillations and waves have been reported in the thalamorecipient auditory cortex in immature animals, with an incidence of 0.4-5 waves/min, and a mean instantaneous firing of 6.4 6 1.3 Hz similar to that observed for TTA-SW in this study [Kotak et al, 2007[Kotak et al, , 2012.…”

“…At the cortical level, pre-wiring of the structures involved in language processing, anatomical/functional asymmetry [Dubois et al, 2008[Dubois et al, , 2014Leroy et al, 2011] and various discrimination abilities [Mahmoudzadeh et al, 2013 are likely to depend on an initial genetic fingerprint. These spontaneous auditory cortical activities in rats and gerbils precede the onset of hearing and gradually disappear following the initiation of sound-evoked response when low-frequency sound cues are first perceived [Kotak et al, 2007[Kotak et al, , 2012. These spontaneous auditory cortical activities in rats and gerbils precede the onset of hearing and gradually disappear following the initiation of sound-evoked response when low-frequency sound cues are first perceived [Kotak et al, 2007[Kotak et al, , 2012.…”

Neuroauditory Toxicity of Artemisinin Combination Therapies—Have Safety Concerns Been Addressed?

“…The peripheral ototoxicity of mefloquine follows a dose-dependent mechanism of cochlear hair cells and spiral ganglion neurons loss different from the artemisinin derivatives 36. However, animal models and a recent human case report have provided additional insight into the clinical significance and plausible pathophysiology of mefloquine focal brainstem, limbic, and thalamic cortical toxicity that needs to be emphasized and further elucidated when investigating the potential neurotoxicity of ACTs 37,38. Cognizant of this information, the US Food and Drug Administration announced label changes for the approved mefloquine hydrochloride in July of 2013 to specifically warn of the risk of permanent neurological effects, including vestibular symptoms and tinnitus 39…”

Formation of cortical inhibition in ontogenesis

“…Recent studies [3][4][5][6][7][8][9][10][11][12][13][14] that changed our concept both of development of inhibitory neurons and of formation of cortical inhibition in ontogenesis in general show that the suggestion made by the above-cited authors is not baseless. Owing to these studies performed mainly by complex methods [3][4][5][6][7][8][9][10][11][12], it was established that the morphofunctional development in their inhibitory neurons and their networks was progressing rapidly.…”

“…Owing to these studies performed mainly by complex methods [3][4][5][6][7][8][9][10][11][12], it was established that the morphofunctional development in their inhibitory neurons and their networks was progressing rapidly. The inhibitory effect of GABA-ergic neurons on other cortex neurons occurred at early periods of their burst activity [4,5].…”