Donata Oertel

Morphology and physiology of cells in slice preparations of the posteroventral cochlear nucleus of mice.

In an effort to understand what integrative tasks are performed in the cochlear nuclei, the present study was undertaken to describe neuronal circuits in the posteroventral cochlear nucleus (PVCN) anatomically and physiologically. The cochlear nuclear complex receives auditory information from the cochlea through the auditory nerve. Within the cochlear nuclei, signals travel along several parallel and interconnected pathways. From the cochlear nuclei, transformed versions of the signals are passed to higher auditory centers in the brainstem. We have recorded electrophysiological responses from cells that were subsequently visualized with horseradish peroxidase (HRP). Responses to shocks to the auditory nerve root and to intracellularly injected current pulses were recorded and correlated with morphology. Two types of stellate cells and octopus cells were distinguished. T stellate cells project out of the cochlear nuclei through the T rapezoid body; D stellate cells do not. The axons of D stellate cells extend D orsalward to the dorsal cochlear nucleus (DCN) but have not been traced out of the nucleus. Both T and D stellate cells have terminal collaterals in the multipolar cell region of the PVCN and in the DCN. The endings of one T stellate cell formed a narrow band rostrocaudally in the fusiform cell layer of the DCN that resembled an isofrequency band. The endings of one D stellate cell lay closely apposed to multipolar cells in the deep layer of the DCN. The dendrites of T stellate cells are often aligned along the path of auditory nerve fibers and end in tufts, whereas those of D stellate cells extend radially in the plane of the lateral surface of the PVCN toward granule cell areas and branch sparingly. Octopus cells have dendrites oriented perpendicularly to the path of auditory nerve fibers. Their axons were cut medially in the slices; none had collateral branches.

Cell-specific, spike timing–dependent plasticities in the dorsal cochlear nucleus

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.

What's a cerebellar circuit doing in the auditory system?

The shapes of the head and ears of mammals are asymmetrical top-to-bottom and front-to-back. Reflections of sounds from these structures differ with the angle of incidence, producing cues for monaural sound localization in the spectra of the stimuli at the eardrum. Neurons in the dorsal cochlear nucleus (DCN) respond specifically to spectral cues and integrate them with somatosensory, vestibular and higher-level auditory information through parallel fiber inputs in a cerebellum-like circuit. Synapses between parallel fibers and their targets show long-term potentiation (LTP) and long-term depression (LTD), whereas those between auditory nerve fibers and their targets do not. This paper discusses the integration of acoustic and the proprioceptive information in terms of possible computational roles for the DCN.

Integrative functions in the mammalian auditory pathway

Introduction.- Summary of Ascending and Descending Auditory Pathways Form the Cochlea.- Biophysical Specializations for Encoding Timing in Brainstem Auditory Nuclei.- Detection of Interaural Time and Intensity Differences for Localization in the Binaural Pathways Through the Brainstem.- The Encoding of Spectral Distortions for Localization in Elevation in the Dorsal Cochlear Nucleus and Inferior Colliculus.- Ascending Pathways Through Monaural Brainstem Nuclei and their Possible Role in Pattern Recognition of Natural Sounds.- Convergence of Brainstem Pathways in the Inferior Colliculus.- Sound Localization by the Auditory Cortex.- Feature Detection by the Auditory Cortex.

Bidirectional synaptic plasticity in the cerebellum-like mammalian dorsal cochlear nucleus

The dorsal cochlear nucleus integrates acoustic with multimodal sensory inputs from widespread areas of the brain. Multimodal inputs are brought to spiny dendrites of fusiform and cartwheel cells in the molecular layer by parallel fibers through synapses that are subject to long-term potentiation and long-term depression. Acoustic cues are brought to smooth dendrites of fusiform cells in the deep layer by auditory nerve fibers through synapses that do not show plasticity. Plasticity requires Ca2+-induced Ca2+ release; its sensitivity to antagonists of N-methyl-d-aspartate and metabotropic glutamate receptors differs in fusiform and cartwheel cells.

Encoding of Timing in the Brain Stem Auditory Nuclei of Vertebrates

Neurons that convey timing of acoustic information in the brain stem of vertebrates have a consistent pattern of anatomical and biophysical specializations. Large synaptic currents produce rapid voltage changes in neurons with low input resistances in the physiological voltage range. In some cells, large synaptic currents are activated through calyceal terminals, while in others, large synaptic currents are activated by the synchronous firing of many inputs through small terminals. Neurotransmitter acts mainly through glutamatergic receptors of the AMPA subtype, whose kinetics are more rapid than in nonauditory neurons.Two interacting voltage-sensitive conductances are of critical functional importance in these cells. Both are activated by small voltage changes away from rest. A mixed cation conductance, Ih, is activated by hyperpolarization. A low-threshold K+ conductance is activated by depolarization. These conductances make synaptic potentials rapid, make firing sensitive to the rate of rise of synaptic excitation, and prevent repetitive firing.Timing information is essential for localizing sound sources and for interpreting the temporal patterns of natural sounds. How timing information is fed through these pathways has already provided insight into how sounds are localized by vertebrates, but much less is known about how these pathways contribute to the interpretation of environmental sounds, including speech. Therein lies the exciting future of this work.

Maturation of synapses and electrical properties of cells in the cochlear nuclei

Auditory nerve fibers carry impulses from the cochlea to the cochlear nuclei. There the temporal firing patterns of auditory nerve fibers are preserved by some cells and altered by others. The two factors which govern how firing patterns are shaped are (1) the intrinsic electrical properties of cells that determine the size and time course of voltage changes caused by synaptic currents and (2) the synaptic circuitry between cells. The electrical properties of cells were measured by recording the responses to current injected intracellularly into brain slice preparations. The synaptic responses to electrical shocks of the auditory nerve were used to determine the functional properties of synaptic connections. The three distinct types of electrical properties of cells that can be distinguished electrophysiologically in similar preparations of mature tissue, bushy and stellate cells in the ventral cochlear nucleus [(1984) J. Neurosci. 4, 1577-1588] and cells in the dorsal cochlear nucleus [Hirsch and Oertel (1987) (submitted); Oertel et al. (1987) In: Functions of the Auditory System, Editor: S. Hassler. J. Wiley and Sons (in press)] can be differentiated at least as early as 7 days after birth. Young cells, however, have higher input resistances and lower input capacitances than mature cells, and they cannot sustain high firing rates. Bushy and stellate cells in the ventral cochlear nucleus respond to electrical stimulation of the auditory nerve with both excitatory and inhibitory postsynaptic potentials as early as 4 days after birth. The synaptic potentials occur with longer and more variable latencies than in mature cells and synapses fatigue more easily, however. Cells of the dorsal cochlear nucleus also receive both excitatory and inhibitory synaptic inputs 4 days after birth, upon stimulation of the auditory nerve. No systematic changes were detected in these synaptic responses as a function of age but this may have been because the variability in the shape and timing of synaptic responses was large even in mature tissue.

Intrinsic properties of neurones in the dorsal cochlear nucleus of mice, in vitro.

1. Intracellular recordings were made from the dorsal cochlear nucleus (DCN) in slices of the cochlear nuclear complex. Probably the larger and most frequent cells were impaled. 2. The steady‐state current‐voltage (I‐V) properties of all cells impaled were nonlinear. The I‐V curve was steepest in the voltage range depolarized from the resting potential and most shallow when the cell was hyperpolarized from rest by more than about 10 mV. Thus, the inwardly rectifying I‐V characteristics of cells in the DCN distinguish them from those of ventral cochlear nuclear neurones (Oertel, 1983). 3. When depolarized with current, most cells fired trains of large, all‐or‐none action potentials. The undershoot after single spikes comprised an initial, fast component followed by a second, slower wave. A few cells (15%) generated bursts of smaller, graded spikes in addition to the large ones. 4. Repetitive firing evoked by depolarizing pulses of current was followed by an after‐hyperpolarization whose magnitude depended on the strength and duration of the preceding current pulse. 5. Blocking the large action potentials with tetrodotoxin (TTX) revealed Ca2+‐dependent spikes in all cells examined. 6. The steady‐state I‐V relationship became linear in the presence of TTX, suggesting that a persistent Na+ conductance probably mediates the inward rectification seen above the resting potential. 7. Muscarine at micromolar concentrations excited cells and increased their input resistance.

Rate thresholds determine the precision of temporal integration in principal cells of the ventral cochlear nucleus.

The three types of principal cells of the ventral cochlear nucleus (VCN), bushy, octopus, and T stellate, differ in the detection of coincidence among synaptic inputs. To explore the role of the action-potential-generation mechanism in the detection of coincident inputs, we examined responses to depolarizing currents that increased at varying rates. To fire an action potential, bushy cells, likely of the globular subtype, had to be depolarized faster than 4.8+/-2.8 mV/ms, octopus cells faster than 9.5+/-3.6 mV/ms, and T stellate cells fired irrespective of the rate of depolarization. The threshold rate of depolarization permitted definition of a time window over which depolarization could contribute to generating action potentials. This integration window differed between cell types. It was 5.3+/-1.8 ms for bushy cells and 1.4+/-0.3 ms for octopus cells. T Stellate cells fired action potentials in response to even slow depolarizations, showing that their integration window was unlimited so that temporal summation in these cells is limited by the time course of synaptic potentials. The rate of depolarization threshold in octopus and bushy cells was decreased by alpha-dendrotoxin while T stellate cells were largely insensitive to alpha-dendrotoxin indicating that low-voltage-activated K+ conductances (gKL) are important determinants of the integration window.

The role of intrinsic neuronal properties in the encoding of auditory information in the cochlear nuclei

It is now possible to relate the intrinsic electrical properties of particular cells in the cochlear nuclei of mammals with their biological function. In the layered dorsal cochlear nucleus, information concerning the location of a sound source seems to be contained in the spatial pattern of activation of a population of neurons. In the unlayered, ventral cochlear nucleus, however, neurons carry information in their temporal firing patterns. The voltage-sensitive conductances that make responses to synaptic current brief enable bushy cells to convey signals from the auditory nerve to the superior olivary complex with a temporal precision of at least 120 microseconds.