No abstract

Acoustic information in auditory nerve discharges is integrated in the cochlear nuclei, and ascends through several parallel pathways to higher centers. Octopus cells of the posteroventral cochlear nucleus form a pathway known to carry information in the timing of action potentials. Octopus cells have dendrites oriented to receive converging input from many auditory nerve fibers. In all 34 intracellular recordings from anatomically identified octopus cells in slices, shocks to the auditory nerve evoked brief, consistent, graded EPSPs. EPSPs were about 1 msec in duration. At all but the lowest shock strengths, the delays between shocks and the peaks of resultant EPSPs had SDs of 0.02 msec. Polysynaptic excitation, perhaps arising from the axon collaterals of octopus cells, was observed. No detectable glycinergic or GABAergic inhibition was evoked with shocks. The input resistances were low, around 10 M omega, voltage changes were rapid, with time constants of about 1 msec, and action potentials were small. The low input resistance resulted in part from a Cs(+)-sensitive conductance. In the presence of 10 or 15 mM extracellular Cs+ the time constants increased 20-fold in the hyperpolarizing voltage range. As several subthreshold inputs were required to produce suprathreshold responses, octopus cells detect the coincident firing of auditory nerve fibers. Under physiological conditions the low input resistance and resulting short time constant limit the time over which temporal summation of excitation from auditory nerve fibers can occur and thus provide temporal precision to electrical signaling.

In the dorsal cochlear nucleus, long-term synaptic plasticity can be induced at the parallel fiber inputs that synapse onto both fusiform principal neurons and cartwheel feedforward inhibitory interneurons. Here we report that in mouse fusiform cells, spikes evoked 5 ms after parallel-fiber excitatory postsynaptic potentials (EPSPs) led to long-term potentiation (LTP), whereas spikes evoked 5 ms before EPSPs led to long-term depression (LTD) of the synapse. The EPSP-spike protocol led to LTD in cartwheel cells, but no synaptic changes resulted from the reverse sequence (spike-EPSP). Plasticity in fusiform and cartwheel cells therefore followed Hebbian and anti-Hebbian learning rules, respectively. Similarly, spikes generated by summing EPSPs from different groups of parallel fibers produced LTP in fusiform cells, and LTD in cartwheel cells. LTD could also be induced in glutamatergic inputs of cartwheel cells by pairing parallel-fiber EPSPs with depolarizing glycinergic PSPs from neighboring cartwheel cells. Thus, synaptic learning rules vary with the postsynaptic cell, and may require the interaction of different transmitter systems.

The anatomical and biophysical specializations of octopus cells allow them to detect the coincident firing of groups of auditory nerve fibers and to convey the precise timing of that coincidence to their targets. Octopus cells occupy a sharply defined region of the most caudal and dorsal part of the mammalian ventral cochlear nucleus. The dendrites of octopus cells cross the bundle of auditory nerve fibers just proximal to where the fibers leave the ventral and enter the dorsal cochlear nucleus, each octopus cell spanning about one-third of the tonotopic array. Octopus cells are excited by auditory nerve fibers through the activation of rapid, calciumpermeable, ␣-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptors. Synaptic responses are shaped by the unusual biophysical characteristics of octopus cells. Octopus cells have very low input resistances (about 7 M⍀), and short time constants (about 200 sec) as a consequence of the activation at rest of a hyperpolarization-activated mixed-cation conductance and a lowthreshold, depolarization-activated potassium conductance. The low input resistance causes rapid synaptic currents to generate rapid and small synaptic potentials. Summation of small synaptic potentials from many fibers is required to bring an octopus cell to threshold. Not only does the low input resistance make individual excitatory postsynaptic potentials brief so that they must be generated within 1 msec to sum but also the voltage-sensitive conductances of octopus cells prevent firing if the activation of auditory nerve inputs is not sufficiently synchronous and depolarization is not sufficiently rapid. In vivo in cats, octopus cells can fire rapidly and respond with exceptionally well-timed action potentials to periodic, broadband sounds such as clicks. Thus both the anatomical specializations and the biophysical specializations make octopus cells detectors of the coincident firing of their auditory nerve fiber inputs.

To determine the correspondence between anatomical and physiological cell types in the ventral cochlear nucleus of the cat, intracellular injections of horseradish peroxidase were made into cells whose extracellular and intracellular responses to sound had been studied. Three identified cells responded to a short tone burst at their characteristic frequencies with an onset pattern. This pattern is characterized by a strong response to the onset of the stimulus. One was an octopus cell. The second cell, located in the octopus-cell area, was a giant cell with a few somatic spines and thin tapering dendrites; the intracellular record revealed that even in the absence of sound it received continuous synaptic input, while tones at characteristic frequency produced a sustained depolarization. A third cell, which had an onset response at low intensities and a chopper response at high intensities, was a stellate cell located in the intermediate acoustic stria with dendrites oriented parallel to the fiber tract. This cell had an unusually broad dynamic range in response to changes in intensity. Two cells with transient chopper response patterns were stellate cells in the posteroventral cochlear nucleus with many branched and beaded dendrites. Three cells with more sustained chopper response patterns were stellate cells in the anteroventral cochlear nucleus with fewer, less-branched, smooth dendrites. Two cells with primarylike responses to tones were bushy cells with numerous short, thin, highly branched dendrites in the posterior division of the anteroventral cochlear nucleus. Intracellular responses to tones at the characteristic frequency consisted of large brief depolarizations, which were not sustained. Another cell, which responded to tones in a phase-locked fashion, was also located in the anteroventral cochlear nucleus. It was a small, stellate cell with relatively few, smooth dendrites. The labeled cells largely support previous attempts at physiological-morphological correlations: (1) bushy cells exhibit primarylike pattern; (2) stellate cells exhibit chopper patterns; and (3) octopus cells exhibit an onset pattern. It was also demonstrated that more than one cell type can exhibit a particular response pattern.