Dietrich W. F. Schwarz

Melody recognition and musical interval perception by deaf subjects stimulated with electrical pulse trains through single cochlear implant electrodes

The perception of musical pitch was investigated in postlinguistically deaf subjects with cochlear implants. Stimuli consisted of sequences of biphasic electrical pulse trains at rates which represented the tones of the equal-tempered musical scale, delivered at equalized comfortable loudness levels to selected single bipolar electrodes along the array of the Nucleus cochlear implant. Seventeen subjects correctly identified a mean of 44% of rhythmically intact familiar tunes, presented in an open-set paradigm. Three subjects were tested with a closed set of melodies without rhythmic cues. The results showed relatively higher recognition scores at lower pulse rates, although melody recognition remained possible up to rates of approximately 600-800 pulses per second. Stimulation of apical electrodes yielded higher recognition scores than of basal electrodes. The perception of musical intervals, defined as frequency ratios between two trains of stimulus pulse rates, was investigated in an interval intonation labeling experiment, for intervals ranging from a minor 3rd to a major 6th. Within a range of low pulse rates, subjects defined the intervals mediated by electrical pulse rate by the same ratios which govern musical intervals of tonal frequencies in normal-hearing listeners. It may be concluded that temporal cues are sufficient for the mediation of musical pitch, at least for the lower half of the range of fundamental frequencies commonly used in music.

Perception of the missing fundamental in nonhuman primates

In preparation for neurophysiological experiments aimed at mechanisms of pitch perception, four rhesus monkeys were trained to press a button when the fundamental frequencies (missing or present) of two complex tones in a tone pair matched. Both tones were based on a five-component harmonic series. Zero to three of the lowest components could be missing in the first tone, while the second (comparison) tone contained all five harmonics. The range of fundamentals tested varied from 200 to 600 Hz. Three monkeys learned to match tones missing their fundamentals to comparison harmonic complexes with the same pitch, whereas the fourth monkey required the physical presence of the fundamental. Consideration of several cues available to the monkeys suggests that the animals could perceive the missing fundamental.

Firing properties of spherical bushy cells in the anteroventral cochlear nucleus of the gerbil

In gerbils, spherical bushy cells (SBCs) encode low frequency sound signals into a temporal firing pattern. To investigate the support for the timing in this temporal code, we characterized the membrane electrical properties of visually identified SBCs in brainstem slices. A brief depolarizing subthreshold transient potential (TP) triggered, with relatively invariant latency, a single spike at the onset of a response to depolarizing current pulses. The activation of a subthreshold Na+-conductance, sensitive to blockade with tetrodotoxin, and a high threshold Ca2+-conductance, sensitive to blockade with Co2+ or Cd2+, accelerated the rising phase and amplified the TP. A K+-conductance, sensitive to blockade by 4-aminopyridine (4-AP, 50 microM), shaped the decay of the TP. Following a single spike, voltage-gated activation of transient and sustained K+-conductances suppressed any tendency to repetitively discharge. A reduction in either K+-conductance due to application of 4-AP or tetraethylammonium (TEA, 10 mM), converted the single spike mode to repetitive firing during the depolarizing pulses. A persistent, tetrodotoxin-sensitive Na+-conductance amplified steady-state depolarizing responses. A hyperpolarization-activated conductance, greatly decreased by extracellular Cs+ (3 mM) but resistant to Ba2+ (up to 1 mM), filtered the responses to hyperpolarizing current inputs. A depolarized membrane potential promoted repetitive firing in SBCs. This state, expected in pathophysiological conditions, would corrupt the temporal code.

Modulation of bursts and high-threshold calcium spikes in neurons of rat auditory thalamus

Neurons in the ventral partition of the medial geniculate body are able to fire high-threshold Ca2+-spikes. The neurons normally discharge such spikes on low-threshold Ca2+-spikes after the action potentials of a burst. We studied membrane mechanisms that regulate the discharge of high-threshold Ca2+-spikes, using whole-cell recording techniques in a slice preparation of rat thalamus. A subthreshold (persistent) Na+-conductance amplified depolarizing inputs, enhancing membrane excitability in the tonic firing mode and amplifying the low-threshold Ca2+-spike in the burst firing mode. Application of tetrodotoxin blocked the amplification and high-threshold Ca2+-spike firing. A slowly inactivating K+ conductance, sensitive to blockade with 4-aminopyridine (50-100 microM), but not tetraethylammonium (2-10 mM), appeared to suppress excitability and high-threshold Ca2+-spike firing. Application of 4-aminopyridine increased the low-threshold Ca2+-spike and the number of action potentials in the burst, and led to a conversion of the superimposed high-threshold Ca2+-spike into a plateau potential. Application of the Ca2+-channel blocker Cd2+ (50 microM), reduced or eliminated this plateau potential. The tetrodotoxin sensitive, persistent Na+-conductance also sustained plateau potentials, triggered after 4-aminopyridine application on depolarization by current pulses. Our results suggest that high-threshold Ca2+-spike firing, and a short-term influx of Ca2+, are regulated by a balance of voltage-dependent conductances. Normally, a slowly inactivating A-type K+-conductance may reduce high-threshold Ca2+-spike firing and shorten high-threshold Ca2+-spike duration. A persistent Na+-conductance promotes coupling of the low-threshold Ca2+-spike to a high-threshold Ca2+-spike. Thus, the activation of both voltage-dependent conductances would affect Ca2+ influx into ventral medial geniculate neurons. This would alter the quality of the different signals transmitted in the thalamocortical system during wakefulness, sleep and pathological states.

Intonation of musical intervals by musical intervals by deaf subjects stimulated with single bipolar cochlear implant electrodes

Some subjects with cochlear implants have been shown to associate electrical stimulus pulse rates with the pitches of musical tones. In order to clarify the role of these pitch sensations in a musical context, the present investigation examined the intonation accuracy achieved by implant subjects when adjusting pulse rates in the reconstruction of musical intervals. Using a method of adjustment, the subjects altered a variable pulse rate, relative to a fixed reference rate, on one electrode, in the tuning of musical intervals abstracted from familiar melodies. At low pulse rates, subjects generally tuned the intervals to the same frequency ratios which define tonal musical intervals in normal-hearing listeners, with error margins comparable to musically untrained subjects. Two subjects were, in addition, able to transpose these melodic intervals from a standard reference pulse rate to higher and lower reference rates (reference and target pulse rates with geometric means of the intervals ranging from 81 to 466 pulses/s). Generally, the intervals were adjusted on a ratio scale, according to the same frequency ratios which define analogous acoustical musical intervals. These results support the hypothesis that, at low pulse rates, a temporal code in the auditory nerve alone is capable of defining musical pitch.

Ketamine blocks non-N-methyl-D-aspartate receptor channels attenuating glutamatergic transmission in the auditory cortex

Objective To investigate the influence of ketamine on non-N-methyl-D-aspartate (NMDA) receptor-mediated synaptic transmission in the auditory cortex. Material and Methods Using whole-cell patch-clamp techniques on pyramidal neurons, we studied the effects of ketamine on excitatory post-synaptic potentials (EPSPs) evoked by electrical stimulation of internal capsule fibers in slices of gerbil auditory cortex. Results After blockade of the slow, NMDA receptor-mediated EPSP component with dl-2-amino-5-phosphonovaleric acid, application of ketamine in a concentration-dependent manner led to a reduction in the amplitude of fast, 6-cyano-7-nitroquinoxalinedione (CNQX)-sensitive EPSPs, accompanied by an increased membrane resistance. Blockade of non-NMDA glutamate receptors with CNQX prevented both effects. Conclusion Ketamine reduces membrane conductance and glutamatergic excitation, in part by blocking alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid receptor channels that may be constitutively active at a low level in slice preparations of auditory cortex.

Metabotropic transmitter actions in auditory thalamus.

Neurons in the ventral partition of the medial geniculate body (MGBv), the primary auditory thalamus, receive afferent input from the inferior colliculus via excitatory glutamate-ergic and inhibitory GABA-ergic input fibres. The feedback from the auditory cortex to the thalamic relay also is mediated via neuron systems using glutamate and GABA as transmitters. We studied effects on excitability mediated by these transmitters via G-protein coupled metabotropic receptors. In a slice preparation of rat thalamus we investigated the membrane responses of MGBv neurons using the whole cell recording technique. Application of a metabotropic glutamate receptor (mGluR) agonist, ACPD (5-100 microM), depolarized MGBv neurons. As a result, the burst mode of firing, which characterizes states of sleep at hyperpolarized potentials was replaced by the tonic mode, which is compatible with sound signal transmission during alertness. The depolarization was caused by an inward current (I(ACPD)) that persisted during blockade of Na+ channels with tetrodotoxin (TTX) and of Ca2+ channels with Cd2+. The I(ACPD) depended, however, on extracellular Na+, which could be replaced with Li+, excluding a major contribution of the Na+/Ca2+ exchange current. ACPD application also inhibited an inwardly rectifying K+ current at hyperpolarized potentials and activated an outward current in the depolarized range. Application of the GABA(B) agonist, baclofen (10 microM), hyperpolarized MGBv neurons by activation of an inwardly rectifying K+ current. The corresponding membrane conductance acted as a powerful shunt that reduced voltage responses and inhibited firing in both the tonic and burst modes. Thus, the effects of GABA(B) receptor activation would suppress auditory signal transfer, whereas mGluR activation enhances excitability, possibly accounting for the alerting effects of certain auditory stimuli.Neurons in the ventral partition of the medial geniculate body (MGBv), the primary auditory thalamus, receive afferent input from the inferior colliculus via excitatory glutamate-ergic and inhibitory GABA-ergic input fibres. The feedback from the auditory cortex to the thalamic relay also is mediated via neuron systems using glutamate and GABA as transmitters. We studied effects on excitability mediated by these transmitters via G-protein coupled metabotropic receptors. In a slice preparation of rat thalamus we investigated the membrane responses of MGBv neurons using the whole cell recording technique. Application of a metabotropic glutamate receptor (mGluR) agonist, ACPD (5-100

Postnatal development of signal generation in auditory thalamic neurons

Using whole cell recording techniques, we distinguished immature from mature stages of development in auditory thalamic neurons of rats at ages P5 to P21. We compared voltage responses to injected currents and firing patterns of neurons in ventral partition of medial geniculate body (MGBv) in slices. Resting potential, input resistance and membrane time constant diminished to mature values between P5 and P14. Responses of young neurons to hyperpolarizing pulses showed delayed inward rectification; after P13, this was obscured by a rapid onset of another inward rectifier. All neurons possessed tetrodotoxin (TTX)-sensitive, depolarization-activated rectification, implying persistent Na+-current involvement. Despite a slightly higher voltage threshold for spiking, the current threshold was lower in younger neurons. Young neurons fired a short latency spike with afterhyperpolarization whereas older neurons exhibited a slow ramplike depolarization before tonic firing. Large currents caused continuous firing in all neurons. Before day P13, a high threshold Ca2+ spike (HTS) often was appended to action potentials. The low threshold Ca2+-spike (LTS) was too small in amplitude to evoke action potentials before P11 but produced a single spike at P12 and P13 and burst firing with HTS after P13. MGBv neurons have mature properties after P14, relevant for reactions to sound and the oscillations of slow-wave sleep.

GABAB receptor activation changes membrane and filter properties of auditory thalamic neurons

Inhibitory inputs from nucleus reticularis thalami and the inferior colliculus activate gamma-aminobutyric acid B (GABA(B)) receptors in auditory thalamic neurons. These metabotropic receptors have been implicated in the oscillatory behavior of thalamic neurons. We studied the effects of the GABA(B) receptor agonist, baclofen, on membrane and filter properties of neurons in the ventral partition of the medial geniculate body (MGBv) of the rat, using whole-cell patch-clamp recording techniques in a slice preparation. Application of baclofen caused a concentration-dependent and reversible hyperpolarization of MGBv neurons. An increase in membrane conductance shunted voltage signals. The shunt suppressed firing in both tonic and burst modes which normally characterize the neuronal excitation from depolarized and hyperpolarized potentials, respectively. The GABA(B) receptor antagonist, CGP 35348 (0.5 mM), completely and reversibly blocked the baclofen-evoked hyperpolarization and increase in conductance. In voltage-clamp and during blockade of synaptic transmission with tetrodotoxin and Cd2+, baclofen activated an inwardly rectifying outward K+ current, that was sensitive to blockade with Ba2+ (0.5 mM). Intracellular applications of GTPgammaS occluded the baclofen current whereas similar applications of GDPbetaS prevented it, suggesting that G-proteins mediated the baclofen current. We measured the impedance amplitude profile in the frequency domain with swept sinusoidal current injection. MGBv neurons normally have lowpass filter characteristics at depolarized potentials and resonance at approximately 1 Hz at hyperpolarized potentials. Baclofen application reduced the impedance below 20 Hz which lowered the membrane filter quality and abolished the resonance. Despite its hyperpolarizing effect, therefore, baclofen eliminated an intrinsic tendency to oscillate as well as the intrinsic frequency selectivity of MGBv neurons.

Firing Modes and Membrane Properties in Lemniscal Auditory Thalamus

In neurons of the auditory thalamus, patterned sequences of action potentials encode the features of sound stimuli. The patterns vary with the membrane potential, characterizing states of wakefulness and sleep. We studied the dependence of the patterns on the membrane potential and specific voltage-gated conductances, using whole-cell patch-clamp recordings from neurons in the ventral medial geniculate body (MGBv) of in vitro slices. Thalamocortical neurons, identified with neurobiotin, exhibited different firing patterns to an excitatory input, depending on the initial membrane potential. From depolarized potentials, the neurons fired in a tonic mode. The delay to firing in this mode was regulated by a balance of persistent Na+ and A-type K+ conductances. When transiently depolarized from hyperpolarized holding potentials, the neurons fired brief phasic responses (burst mode). Phasic responses were induced by low threshold Ca2+ spikes (LTSs); the LTS-amplitude was controlled by Na+ and K+ conductances. Under favourable conditions, an LTS triggered more than one action potential and one or more high threshold Ca2+ spikes (HTSs). Consciously perceived sound signals are transmitted in the tonic mode. During sleep, alerting stimuli may interact with membrane non-linearities, converting hyperpolarized bursting MGBv neurons to the tonic mode.