Species-Specific Adaptation for Ongoing High-Frequency Action Potential Generation in MNTB Neurons.

Comparative analysis of evolutionarily conserved neuronal circuits between phylogenetically distant mammals highlights the relevant mechanisms and specific adaptations to information processing. The medial nucleus of the trapezoid body (MNTB) is a conserved mammalian auditory brainstem nucleus relevant for temporal processing. While MNTB neurons have been extensively investigated, a comparative analysis of phylogenetically distant mammals and the spike generation is missing. To understand the suprathreshold precision and firing rate, we examined the membrane, voltage-gated ion channel and synaptic properties in Phyllostomus discolor (bat) and in Meriones unguiculatus (rodent) of either sex. Between the two species, the membrane properties of MNTB neurons were similar at rest with only minor differences, while larger dendrotoxin (DTX)-sensitive potassium currents were found in gerbils. Calyx of Held-mediated EPSCs were smaller and frequency dependence of short-term plasticity (STP) less pronounced in bats. Simulating synaptic train stimulations in dynamic clamp revealed that MNTB neurons fired with decreasing success rate near conductance threshold and at increasing stimulation frequency. Driven by STP-dependent conductance decrease, the latency of evoked action potentials increased during train stimulations. The spike generator showed a temporal adaptation at the beginning of train stimulations that can be explained by sodium current inactivation. Compared with gerbils, the spike generator of bats sustained higher frequency input-output functions and upheld the same temporal precision. Our data mechanistically support that MNTB input-output functions in bats are suited to sustain precise high-frequency rates, while for gerbils, temporal precision appears more relevant and an adaptation to high output-rates can be spared.SIGNIFICANCE STATEMENT Neurons in the mammalian medial nucleus of the trapezoid body (MNTB) convey precise, faithful inhibition vital for binaural hearing and gap detection. The MNTB's structure and function appear evolutionarily well conserved. We compared the cellular physiology of MNTB neurons in bat and gerbil. Because of their adaptations to echolocation or low frequency hearing both species are model systems for hearing research, yet with largely overlapping hearing ranges. We find that bat neurons sustain information transfer with higher ongoing rates and precision based on synaptic and biophysical differences in comparison to gerbils. Thus, even in evolutionarily conserved circuits species-specific adaptations prevail, highlighting the importance for comparative research to differentiate general circuit functions and their specific adaptations.

Developmental profile of microglia distribution in nuclei of the superior olivary complex.

In the brain, microglia are involved in immune responses and synaptic maturation. During early development, these cells invade the brain, proliferate, and morphologically mature to achieve coverage of the surrounding tissue with their fine processes. Their developmental proliferation overlaps with the postnatal development of neuronal circuits. Within the superior olivary complex (SOC), an auditory brainstem structure, microglia, and their early postnatal development have been documented. A quantification over the full developmental profile of the arrangement and morphological changes in single microglia cells is missing. Here, we used immunofluorescence labeling to quantify their distribution, morphological changes, and coverage during early and late postnatal development in the SOC of Mongolian gerbils. Microglia distributed rather homogenously within each nucleus with a bias to the nucleus borders at postnatal day (P) 5 and more centrally in the nucleus in mature stages. We found a nucleus-specific transient increase in microglia cell number and density reaching its peak at P17 with a subsequent decline to P55 values. Length and branching of microglia protrusions increased especially after P12. The stronger ramification together with the increase in cell density allows coverage of the surrounding tissue from P5 to mature stages, despite the large developmental increase in nucleus size. The transient increase in density during synaptic refinement in SOC nuclei suggests that microglia are important during the pruning period, compensating for developmental increase in tissue volume, and that in mature stages their main function appears tissue surveillance.