Biology subjects

Gartside, S. E.

Publications and source records attributed to Gartside, S. E..

3 recordsLinked to original sources

bioRxiv2023

Motor, somatosensory, and executive cortical areas directly modulate firing activity in the auditory midbrain

We have recently reported that the central nucleus of the inferior colliculus (the auditory midbrain) is innervated by glutamatergic pyramidal cells originating not only in auditory cortex (AC) but also in multiple non-auditory regions of the cerebral cortex. Using optogenetics and electrical stimulation, we investigated the functional properties of these descending connections in vivo in anaesthetised rats. A retrograde virus encoding green fluorescent protein (GFP) and channelrhodopsin (ChR2) injected into the central nucleus of the inferior colliculus (ICC), labelled discrete groups of cells in multiple areas of the cerebral cortex. Light stimulation of AC and M1 caused local activation of cortical neurones and increased the firing rate of neurones in ICc indicating a direct excitatory input from AC and M1 to ICC. Electrical stimulation of M1, secondary motor, somatosensory and prefrontal cortical regions evoked short, fixed latency firing events in ICC as well as longer latency, longer duration increases in firing activity. The short latency events were singular spikes of consistent shape and size likely resulting from monosynaptic excitation of individual ICC units. The longer latency responses comprised multiple units and spikes occurred with significant temporal jitter suggesting polysynaptic activation of local circuits within the ICC. The probability of the monosynaptic event, the magnitude of the polysynaptic response, and the area of ICC affected were dependent on the stimulus current. Our data are consistent with cortical regions exerting an important excitatory direct and indirect regulation of ICc neurones. Significance statementWe have recently described inputs from motor, somatosensory, and executive cortices to the inferior colliculus (IC, auditory midbrain). Here we provide functional evidence for such connections. Optogenetics, using a retrograde virus encoding channelrhodopsin injected into IC revealed a direct excitatory influence of neurones in auditory and motor cortices on firing in IC. Electrical stimulation of discrete cortical regions revealed that multiple non-auditory cortical regions have a direct monosynaptic excitatory influence on neurones in the IC which, in turn, activates local circuits increasing the firing probability of multiple neurones in the IC. This is the first evidence for circuitry by which auditory processing can be influenced at an early stage by activity in the sensory, motor and executive domains.

neuroscience↗

bioRxiv2021

Nitric oxide signalling underlies salicylate-induced increases in neuronal firing in the inferior colliculus: a central mechanism of tinnitus?

The tinnitus-inducing agent salicylate reduces cochlear output but causes hyperactivity in higher auditory centres, including the inferior colliculus (the auditory midbrain). Using multi-electrode recording in anaesthetised guinea pigs (Cavia porcellus), we addressed the hypothesis that salicylate-induced hyperactivity in the inferior colliculus involves nitric oxide signalling secondary to increased ascending excitatory input. In the inferior colliculus, systemic salicylate (200 mg/kg i.p., 0 h) markedly increased spontaneous and sound-driven neuronal firing (3-6 h post drug) with both onset and sustained responses to pure tones being massively increased. Reverse microdialysis of increasing concentrations of salicylate directly into the inferior colliculus (100 {micro}M-10 mM, from 0 h) failed to mimic systemic salicylate. In contrast, it caused a small, transient, increase in sound-driven firing (1 h), followed by a larger sustained decrease in both spontaneous and sound-driven firing (2-5 h). When salicylate was given systemically, reverse microdialysis of the neuronal nitric oxide synthase inhibitor L-methyl arginine into the inferior colliculus (500 mM, 2-6 h) completely blocked the salicylate-induced increase in spontaneous and sound-driven neuronal firing. Our data indicate that systemic salicylate induces neuronal hyperactivity in the auditory midbrain via a mechanism outside the inferior colliculus, presumably upstream in the auditory pathway; and that the mechanism is ultimately dependent on nitric oxide signalling within the inferior colliculus. Given that nitric oxide is known to mediate NMDA receptor signalling in the inferior colliculus, we propose that salicylate activates an ascending glutamatergic input to the inferior colliculus and that this is an important mechanism underlying salicylate-induced tinnitus. Graphical abstractTinnitus is associated with increased activity in the central auditory pathway, an effect replicated by high dose sodium salicylate. Here we show that salicylate-induced increases in neuronal activity in the auditory midbrain are mediated by nitric oxide signalling within this region. Nitric oxide is a key mediator of neuronal responses to NMDA receptor stimulation in this region. Our data support the hypothesis that tinnitus is mediated by increased ascending glutamatergic input to the auditory midbrain. O_FIG O_LINKSMALLFIG WIDTH=160 HEIGHT=200 SRC="FIGDIR/small/444151v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@1d732dcorg.highwire.dtl.DTLVardef@14c2314org.highwire.dtl.DTLVardef@1930a33org.highwire.dtl.DTLVardef@82d799_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2019

Multiple non-auditory cortical regions innervate the auditory midbrain

Our perceptual experience of sound depends on the integration of multiple sensory and cognitive domains, but the networks sub-serving this integration are unclear. There are connections linking different cortical domains, however we do not know if there are also connections between multiple cortical domains and subcortical structures. Retrograde tracing in rats revealed that the inferior colliculus - the auditory midbrain - receives dense descending projections from not only the auditory cortex, but also the visual, somatosensory, motor, and prefrontal cortices. While all these descending connections are bilateral, those from sensory areas show a more pronounced ipsilateral dominance than those from motor and prefrontal cortices. Anterograde tracing from cortical areas identified by retrograde tracing, showed cortical fibres terminating in all three subdivisions of the inferior colliculus, targeting both inhibitory and excitatory neurons. These findings demonstrate that auditory perception is served by a network that includes extensive descending connections from sensory, behavioural, and executive cortices.

neuroscience↗