Transient gain adjustment in the inferior colliculus is serotonin- and calcium-dependent

Abstract

In the inferior colliculus (IC), a brief period of acoustic conditioning can transiently enhance evoked discharge rate. The cellular basis of this phenomenon was assessed with whole cell current-clamp recordings in a gerbil IC brain slice preparation. The current needed to elicit a single action potential was first established for each neuron. A 5s synaptic stimulus train was delivered to the lateral lemniscus (LL), and followed immediately by the initial current pulse to assess a change in postsynaptic gain. The majority of IC neurons (66%) displayed an increase in current-evoked action potentials (positive gain). Despite the blockade of ionotropic glutamate receptors, this effect was correlated with membrane depolarization that occurred during the synaptic train. The postsynaptic mechanism for positive gain was examined by selective blockade of specific neurotransmitter receptors. Gain in action potentials was enhanced by antagonists of metabotropic glutamate, acetylcholine, GABA A and glycine receptors. In contrast, the gain was blocked or reduced by an antagonist to ionotropic serotonin receptors (5-HT 3 R). Blocking voltage-activated calcium channels with verapamil also reduced the effect. These results suggest that 5-HT 3 R activation, coupled with increased intracellular calcium, can transiently alter postsynaptic excitability in IC neurons.

Age-related changes in envelope-following responses at equalized peripheral or central activation

“…In addition, our previous work and other studies have shown that central auditory neurons may adjust their gain in aged animals to compensate for diminished AN input [Parthasarathy et al, 2014, Kotak and Sanes, 2003, Miko and Sanes, 2009]. Hence, to account for age-related differences in central gain, we attempted to equate central neural activation in a separate test by matching EFR amplitudes in young and aged animals.…”

“…Hence, we attempted to equate peripheral activation by adjusting sound levels in young animals to match to aged animals’ median tone 8 kHz ABR wave I amplitudes at 85 dB pSPL. In addition to age-related changes in the auditory periphery, gain of the central auditory system has also been reported to increase to compensate for reduced ANF activation in aging [Parthasarathy et al, 2014, Kotak and Sanes, 2003, Miko and Sanes, 2009]. Therefore, we attempted to match central population activation by matching the young EFRs to the median of the aged EFRs evoked by 100 % depth AM tones at 85 dB SPL.…”

Age-Related Changes in Processing Simultaneous Amplitude Modulated Sounds Assessed Using Envelope Following Responses

“…More information regarding the actual pattern of synaptopathy seen with age will lead to a better refinement of the model to accurately reproduce the EFRs. Central processing changes in aging and other forms of hearing loss manifest as decreases in inhibition (Caspary et al 2008) as well as changes in excitation due to compensatory mechanisms reacting to the reduced peripheral input (Cui et al 2007;Miko and Sanes 2009). However, these compensatory mechanisms come at the cost of reduced synchrony of neural representations (Rabang et al 2012).…”

Metabotropic glutamate receptors in auditory processing

“…1D). Blocking mGluRs with a non-specific antagonist MCPG increases the gain in action potential firing of IC neurons (Miko and Sanes, 2009). Antagonism but not activation of group II mGluRs also increases firing of IC neurons in vivo (Voytenko and Galazyuk, 2011), suggesting suppression of cellular excitability by endogenous activity of group II mGluRs.…”