Norepinephrine enhances song responsiveness and encoding in the auditory forebrain of male zebra finches

Abstract

Norepinephrine (NE) can dynamically modulate excitability and functional connectivity of neural circuits in response to changes in external and internal states. Regulation by NE has been demonstrated extensively in mammalian sensory cortices, but whether NE-dependent modulation in sensory cortex alters response properties in downstream sensorimotor regions is less clear. Here we examine this question in male zebra finches, a songbird species with complex vocalizations and a well-defined neural network for auditory processing of those vocalizations. We test the hypothesis that NE modulates auditory processing and encoding, using paired extracellular electrophysiology recordings and pattern classifier analyses. We report that a NE infusion into the auditory cortical region NCM (caudomedial nidopallium; analogous to mammalian secondary auditory cortex) enhances the auditory responses, burst firing, and coding properties of single NCM neurons. Furthermore, we report that NE-dependent changes in NCM coding properties, but not auditory response strength, are transmitted downstream to the sensorimotor nucleus HVC. Finally, NE modulation in the NCM of males is qualitatively similar to that observed in females: in both sexes, NE increases auditory response strengths. However, we observed a sex difference in the mechanism of enhancement: whereas NE increases response strength in females by decreasing baseline firing rates, NE increases response strength in males by increasing auditory-evoked activity. Therefore, NE signaling exhibits a compensatory sex difference to achieve a similar, state-dependent enhancement in signal-to-noise ratio and coding accuracy in males and females. In summary, our results provide further evidence for adrenergic regulation of sensory processing and modulation of auditory/sensorimotor functional connectivity. NEW & NOTEWORTHY This study documents that the catecholamine norepinephrine (also known as noradrenaline) acts in the auditory cortex to shape local processing of complex sound stimuli. Moreover, it also enhances the coding accuracy of neurons in the auditory cortex as well as in the downstream sensorimotor cortex. Finally, this study shows that while the sensory-enhancing effects of norepinephrine are similar in males and females, there are sex differences in the mode of action.

Context-Dependent Relationships between Locus Coeruleus Firing Patterns and Coordinated Neural Activity in the Anterior Cingulate Cortex

“…However, these changes in single-unit ACC responses were not related reliably to properties of the concurrently measured LC response that we could measure and thus may involve mechanisms other than the LC-NE system. These findings do not appear to be consistent with previous work showing improvements in signal-to-noise ratios in cortex in response to LC-NE activation or during states of higher versus lower global arousal (Kolta et al, 1978;Mclean and Waterhouse, 1994;Lee et al, 2018;Lombardo et al, 2018). This difference could reflect differences in the specific neurons that we targeted in ACC, the different task conditions we tested relative to previous studies, or both, and also merits further study.…”

Silence, Solitude, and Serotonin: Neural Mechanisms Linking Hearing Loss and Social Isolation

“…At the level of auditory circuitry, neuromodulators regulate the balance of excitatory and inhibitory pathways through presynaptic and postsynaptic mechanisms [ 53 , 54 , 55 , 56 , 57 ]. As a result, neuromodulators alter the ways that auditory neurons respond to acoustic stimuli ([ 58 , 59 , 60 ]; reviewed in [ 52 ]) and gate information from different sources through key circuit elements like projection neurons [ 56 , 61 ]. Neuromodulatory neurons may receive afferent information from a wide range of integrative brain systems, and therefore, have the potential to provide ‘value-added’ feedback to the auditory system.…”

Noise exposure alters MMP9 and brevican expression in the rat primary auditory cortex

“…This study used female mice. Because it has been suggested that the auditory cortical responses during auditory stimulation including noise have sex-differences [33,34], the possible differences in male are warrant to be considered.…”