Although the visual circuits in the superior colliculus (SC) have been thoroughly examined, the auditory circuits lack equivalent scrutiny. SC neurons receiving auditory inputs in mice were characterized and three distinguishable types of neurons were found. The auditory pathways from external nuclei of the inferior colliculus (IC) were characterized, and a novel direct inhibitory connection and an excitation that drives feed-forward inhibitory circuits within the SC were found. The direct excitatory and inhibitory inputs exhibited distinct arbourization patterns in the SC. These findings suggest functional differences between excitatory and inhibitory sensory information that targets the auditory SC.

The integration of excitatory and inhibitory synaptic inputs is fundamental to neuronal processing. In the mammalian auditory brainstem, neurons compare excitatory and inhibitory inputs from the ipsilateral and contralateral ear, respectively, for sound localization. However, the temporal precision and functional roles of inhibition in this integration process are unclear. Here, we demonstrate by in vivo recordings from the lateral superior olive (LSO) that inhibition controls spiking with microsecond precision throughout high frequency click trains. Depending on the relative timing of excitation and inhibition, neuronal spike probability is either suppressed or-unexpectedly-facilitated. In vitro conductance-clamp LSO recordings establish that a reduction in the voltage threshold for spike initiation due to a prior hyperpolarization results in post-inhibitory facilitation of otherwise sub-threshold synaptic events. Thus, microsecond-precise differences in the arrival of inhibition relative to excitation can facilitate spiking in the LSO, thereby promoting spatial sensitivity during the processing of faint sounds.

High-frequency stimulation leads to a transient increase in the amplitude of evoked synaptic transmission that is known as posttetanic potentiation (PTP). Here we examine the roles of the calcium-dependent protein kinase C isoforms PKCα and PKCβ in PTP at the calyx of Held synapse. In PKCα/β double knockouts, 80% of PTP is eliminated, whereas basal synaptic properties are unaffected. PKCα and PKCβ produce PTP by increasing the size of the readily releasable pool of vesicles evoked by high-frequency stimulation and by increasing the fraction of this pool released by the first stimulus. PKCα and PKCβ do not facilitate presynaptic calcium currents. The small PTP remaining in double knockouts is mediated partly by an increase in miniature excitatory postsynaptic current amplitude and partly by a mechanism involving myosin light chain kinase. These experiments establish that PKCα and PKCβ are crucial for PTP and suggest that long-lasting presynaptic calcium increases produced by tetanic stimulation may activate these isoforms to produce PTP.

One hallmark of adult neurogenesis is its adaptability to environmental influences. Here, we uncovered the epithelial sodium channel (ENaC) as a key regulator of adult neurogenesis as its deletion in neural stem cells (NSCs) and their progeny in the murine subependymal zone (SEZ) strongly impairs their proliferation and neurogenic output in the olfactory bulb. Importantly, alteration of fluid flow promotes proliferation of SEZ cells in an ENaC-dependent manner, eliciting sodium and calcium signals that regulate proliferation via calcium-release-activated channels and phosphorylation of ERK. Flow-induced calcium signals are restricted to NSCs in contact with the ventricular fluid, thereby providing a highly specific mechanism to regulate NSC behavior at this special interface with the cerebrospinal fluid. Thus, ENaC plays a central role in regulating adult neurogenesis, and among multiple modes of ENaC function, flow-induced changes in sodium signals are critical for NSC biology.