High concentrations of divalent cations isolate monosynaptic inputs from local circuits in the auditory midbrain

Abstract

Hierarchical processing of sensory information occurs at multiple levels between the peripheral and central pathway. Different extents of convergence and divergence in top down and bottom up projections makes it difficult to separate the various components activated by a sensory input. In particular, hierarchical processing at sub-cortical levels is little understood. Here we have developed a method to isolate extrinsic inputs to the inferior colliculus (IC), a nucleus in the midbrain region of the auditory system, with extensive ascending and descending convergence. By applying a high concentration of divalent cations (HiDi) locally within the IC, we isolate a HiDi-sensitive from a HiDi-insensitive component of responses evoked by afferent input in brain slices and in vivo during a sound stimulus. Our results suggest that the HiDi-sensitive component is a monosynaptic input to the IC, while the HiDi-insensitive component is a local polysynaptic circuit. Monosynaptic inputs have short latencies, rapid rise times, and underlie first spike latencies. Local inputs have variable delays and evoke long-lasting excitation. In vivo, local circuits have variable onset times and temporal profiles. Our results suggest that high concentrations of divalent cations should prove to be a widely useful method of isolating extrinsic monosynaptic inputs from local circuits in vivo.

Local and commissural IC neurons make axosomatic inputs on large GABAergic tectothalamic neurons

“…Thus, there is a complex convergence of local and ascending inputs on neurons in the IC that creates a complex internal microcircuitry. Recent physiological studies have emphasized the importance of the local connections within the IC for the neural processing of sound (Chandrasekaran et al, 2013; Grimsley et al, 2013; Sivaramakrishnan et al, 2013). Nevertheless, little is known about how specific neuron types in the IC contribute to the local microcircuitry.…”

Midbrain local circuits shape sound intensity codes

“…The convergence that results from the recruitment of auditory afferent inputs with sound pressure level (Sachs and Abbas, 1974) is inadequate to cover the ~110 dB range of normal hearing (Spirou et al, 1999; Young and Sachs, 2008), implying that ascending input alone is insufficient to generate a monotonically increasing firing rate over the whole intensity range. In the midbrain nucleus of the inferior colliculus (IC), afferent lemniscal activation in brain slices recruits local circuits that prolong synaptic responses (Sivaramakrishnan et al, 2013). At high levels of afferent recruitment, synaptic potentials have prolonged plateau depolarizations that increase the duration and rate of firing (Sivaramakrishnan et al, 2004; Sivaramakrishnan and Oliver, 2006).…”

“…The central nucleus of the IC receives massive input convergence from lower auditory nuclei and corticofugal projections, and local circuits connect layers of cells that receive inputs at different frequencies (Oliver et al, 1991, 1997; Chase and Young, 2005; Chandrasekaran et al, 2013). To test the role of local circuits in forming codes of sound intensity, we applied a high concentration of divalent cations (HiDi; raised Ca 2 + and Mg 2 + concentrations; Frankenhaeuser and Hodgkin, 1957) locally in the IC during changes in sound intensity, to isolate monosynaptic from local inputs (Sivaramakrishnan et al, 2013). We found that as sound intensity increased, the source of recruited synapses changed from monosynaptic to local.…”

Response features across the auditory midbrain reveal an organization consistent with a dual lemniscal pathway

“…In addition to brain stem inputs, local midbrain projections may target and interact with neurons differentially across an ICC lamina that could result in subregions with different functional properties. A recent study that differentiated between monosynaptic inputs from local polysynaptic inputs within the inferior colliculus found that monosynaptic inputs have short latencies, whereas local polysynaptic inputs result in variable onset times and evoke long-lasting excitation (Sivaramakrishnan et al 2013). Together with our results showing that caudal-and-medial regions respond with longer, more diverse latencies and longer PSTH durations than rostral-and-lateral regions, this suggests that local polysynaptic midbrain circuits may be targeting and activating the caudal-and-medial regions to a larger extent.…”