Clifford H. Keller

Na+ channel accumulation on axolemma of afferent endings in nerve end neuromas in Apteronotus

In mammals, cut sensory axons trapped in a nerve end neuroma have been shown to develop hyperexcitability, and to become a source of ectopic afferent discharge and abnormal sensation. We have explored cellular mechanisms underlying neuroma electrogenesis. First we confirmed that ectopic neuroma discharge develops in injured afferents in the electrosensory lateral line nerve of the weakly electric fish Apteronotus, as it does in mammals. Then, using previously characterized antibodies that specifically recognize Na+ channel proteins in this species, we obtained light and electron microscopic evidence of abnormally intense immunolabelling of axolemma at the injury site. Accumulation of excess Na+ channels in afferent endings in neuromas could account for their electrical hyperexcitability.

Motor control of the jamming avoidance response of Apteronotus leptorhynchus: evolutionary changes of a behavior and its neuronal substrates

The two closely related gymnotiform fishes, Apteronotus and Eigenmannia, share many similar communication and electrolocation behaviors that require modulation of the frequency of their electric organ discharges. The premotor linkages between their electrosensory system and their medullary pacemaker nucleus, which controls the repetition rate of their electric organ discharges, appear to function differently, however. In the context of the jamming avoidance response, Eigenmannia can raise or lower its electric organ discharge frequency from its resting level. A normally quiescent input from the diencephalic prepacemaker nucleus can be recruited to raise the electric organ discharge frequency above the resting level. Another normally active input, from the sublemniscal prepacemaker nucleus, can be inhibited to lower the electric organ discharge frequency below the resting level (Metzner 1993). In contrast, during a jamming avoidance response, Apteronotus cannot lower its electric organ discharge frequency below the resting level. The sublemniscal prepacemaker is normally completely inhibited and release of this inhibition allows the electric organ discharge frequency to rise during the jamming avoidance response. Further inhibition of this nucleus cannot lower the electric organ discharge frequency below the resting level. Lesions of the diencephalic prepacemaker do not affect performance of the jamming avoidance response. Thus, in Apteronotus, the sublemniscal prepacemaker alone controls the change of the electric organ discharge frequency during the jamming avoidance response.

The control of pacemaker modulations for social communication in the weakly electric fish Sternopygus

SummaryNearly sinusoidal electric organ discharges (EODs) of the weakly electric fish Sternopygus, occur at a regular rate within a range from 50 to 200 Hz and are commanded by a medullary pacemaker nucleus (Pn). During courtship and aggression, the rate of EODs is modulated as smooth EOD-frequency rises or brief EOD-interruptions (Hopkins 1974b). The present study examines the control of such modulations. Rises were elicited by L-glutamate stimulation of the diencephalic prepacemaker nucleus, the only previously known source of input to the Pn. We demonstrate an additional input to the Pn, the sublemniscal prepacemaker nucleus (SPPn). L-glutamate stimulation of this area caused EOD-interruptions.The Pn contains electrotonically coupled ‘pacemaker cells’ which generate the rhythm of the EODs, as well as ‘relay cells’ which transmit the command pulse to the spinal motor neurons that innervate the electric organ. Pacemaker cells recorded intracellularly during EOD-interruptions continued firing at their regular frequency but with slightly increased jitter. Relay cells, on the other hand, were strongly depolarized and fired spikelets at a greatly increased frequency during EOD-interruptions. Thus EOD-interruptions were caused by SPPn input to relay cells that caused their massive depolarization, blocking the normal input from pacemaker cells without greatly affecting pacemaker cell firing characteristics.Application to the Pn of an antagonist to NMDA-type glutamate receptors blocked EOD-frequency rises and EOD-interruptions. Antagonists to quisqualate/ kainate receptor-types were ineffective.

Hormone-induced and maturational changes in electric organ discharges and electroreceptor tuning in the weakly electric fishApteronotus

SummaryPlasticity in the frequency of the electric organ discharge (EOD) and electroreceptor tuning of weakly electric fish was studied in the genusApteronotus. Both hormone-induced and maturational changes in EOD frequency and electroreceptor tuning were examined.Apteronotus is different from all other steroid-responsive weakly electric fish in that estradiol-17β, rather than androgens, induces discharge frequency decreases. This result can account for the ‘reversed’ discharge frequency dimorphism found inApteronotus in which, counter to all other known sexually dimorphic electric fish, females have lower discharge frequencies than males. Studies of electroreceptor tuning inApteronotus indicate that electroreceptors are closely tuned to the frequency of the EOD. This finding was noted not only in adult animals, but also in juvenile animals shortly after the onset of their EODs. Tuning plasticity inApteronotus, as in other species studied, is associated with altered EOD frequencies and was noted in both maturational EOD changes and in estrogen-induced changes. Thus, tuning plasticity appears to be a general phenomenon which occurs concurrent with a variety of EOD changes.

Responses to simulated echoes by neurons in the barn owl's auditory space map.

The natural acoustical environment contains many reflective surfaces that give rise to echoes, complicating the task of sound localization and identification. The barn owl (Tyto alba), as a nocturnal predator, relies heavily on its auditory system for tracking and capturing prey in this highly echoic environment. The external nucleus of the owls inferior colliculus (ICx) contains a retina-like map of space composed of “space-specific” auditory neurons that have spatially limited receptive fields. We recorded extracellularly from individual space-specific neurons in an attempt to understand the pattern of activity across the ICx in response to a brief direct sound and a simulated echo. Space-specific neurons responded strongly to the direct sound, but their response to a simulated echo was suppressed, typically, if the echo arrived within 5 ms or less of the direct sound. Thus we expect there to be little or no representation within the ICx of echoes arriving within such short delays.Behavioral tests using the owls natural tendency to turn their head toward a sound source suggested that owls, like their space-specific neurons, similarly localize only the first of two brief sounds. Naive, untrained owls were presented with a pair of sounds in rapid succession from two horizontally-separated speakers. With interstimulus delays of less than 10 ms, the owl consistently turned its head toward the leading speaker. Longer delays elicited head turns to either speaker with approximately equal frequency and in some cases to both speakers sequentially.

Structure and function of neurons in the complex of the nucleus electrosensorius of the gymnotiform fish Eigenmannia: Detection and processing of electric signals in social communication

SummaryThe complex of the diencephalic nucleus electrosensorius (nE) provides an interface between the electrosensory processing performed by the torus semicircularis and the control of specific behavioral responses. The rostral portion of the nE comprises two subdivisions that differ in the response properties and projection patterns of their neurons. First, the nEb (Fig. 1 B), which contains neurons that are driven almost exclusively by beat patterns generated by the interference of electric organ discharges (EODs) of similar frequencies. Second, the area medial to the nEb, comprising the lateral pretectum (PT) and the nE-acusticolateralis region (nEar, Fig. 1 B-D), which contains neurons excited predominantly by EOD interruptions, signals associated with aggression and courtship. Neurons in the second area commonly receive convergent inputs originating from ampullary and tuberous electroreceptors, which respond to the low-frequency and high-frequency components of EOD interruptions, respectively. Projections of these neurons to hypothalamic areas linked to the pituitary may mediate modulations of a fishs endocrine state that are caused by exposure to EOD interruptions of its mate.

Head-related transfer functions of the Rhesus monkey

Head-related transfer functions (HRTFs) are direction-specific acoustic filters formed by the head, the pinnae and the ear canals. They can be used to assess acoustical cues available for sound localization and to construct virtual auditory environments. We measured the HRTFs of three anesthetized Rhesus monkeys (Macaca mulatta) from 591 locations in the frontal hemisphere ranging from -90 degrees (left) to 90 degrees (right) in azimuth and -60 degrees (down) to 90 degrees (up) in elevation for frequencies between 0.5 and 15 kHz. Acoustic validation of the HRTFs shows good agreement between free field and virtual sound sources. Monaural spectra exhibit deep notches at frequencies above 9 kHz, providing putative cues for elevation discrimination. Interaural level differences (ILDs) and interaural time differences (ITDs) generally vary monotonically with azimuth between 0.5 and 8 kHz, suggesting that these two cues can be used to discriminate azimuthal position. Comparison with published subsets of HRTFs from squirrel monkeys (Saimiri sciureus) shows good agreement. Comparison with published human HRTFs from the frontal hemisphere demonstrates overall similarity in the patterns of ILD and ITD, suggesting that the Rhesus monkey is a good acoustic model for these two sound localization cues in humans. Finally, the measured ITDs in the horizontal plane agree well between -40 degrees and 40 degrees in azimuth with those calculated from a spherical head model with a radius of 52 mm, one-half the interaural distance of the monkey.

The synthesis and use of the owl's auditory space map

Abstract.The barn owl (Tyto alba) is capable of capturing prey by passive hearing alone, guided by a topographic map of auditory space in the external nucleus of its inferior colliculus. The neurons of this auditory space map have discrete spatial receptive fields that result from the computation of interaural differences in the level (ILD) and time-of-arrival (ITD) of sounds. Below we review the synthesis of the spatial receptive fields from the frequency-specific ITDs and ILDs to which the neurons are tuned, concentrating on recent studies exploiting virtual auditory space techniques to analyze the contribution of ILD. We then compared the owl’s spatial discrimination, assessed behaviorally, with that of its space map neurons. Spatial discrimination was assessed using a novel paradigm involving the pupillary dilation response (PDR), and neuronal acuity was assessed by measuring the changes in firing rate resulting from changes in source location, scaled to the variance. This signal-detection-based approach revealed that the change in the position of the neural image on this map best explains the spatial discrimination measured using the PDR. We compare this result to recent studies in mammalian systems.

From distributed sensory processing to discrete motor representations in the diencephalon of the electric fish, Eigenmannia.

SummaryDuring their jamming avoidance response (JAR), weakly electric fish of the genusEigenmannia shift their electric organ discharge (EOD) frequency away from a similar EOD frequency of a neighboring fish. The behavioral rules and neural substrates for stimulus recognition and motor control of the JAR have been extensively studied (see review by Heiligenberg 1986). The diencephalic nucleus electrosensorius (nE) links sensory processing within the torus semicircularis and optic tectum with the mesencephalic prepacemaker nucleus which, in turn, modulates the medullary pacemaker nucleus and hence the EOD frequency. Two separate areas within the nE responsible for JAR-related EOD frequency rises and frequency falls, respectively, were identified by iontophoresis of the excitatory amino acid L-glutamate. Bilateral lesion of the areas causing EOD frequency rises resulted in elimination of JAR-related frequency rises above a baseline frequency obtained in the absence of a jamming stimulus. Similarly, bilateral lesion of the areas causing frequency falls resulted in a loss of JAR-related frequency falls below the baseline frequency. Whether these areas are also responsible for non-JAR-related frequency shifts is not known. The strength of response and spatial extent of the areas causing frequency shifts varied among fish and also varied in individual fish, reflecting the strength of JAR-related frequency shifts and the balance of activities in frequency-rise and frequency-fall areas. Local application of bicuculline-methiodide or GABA demonstrated a tonic inhibitory input to each area and suggests a reciprocal inhibitory interaction between the two ipsilateral areas, possibly accounting for much of the individual plasticity.The nE thus is a site for neuronal transformation from distributed, topographically organized processing within the laminated structures of the torus and tectum to discrete cell clusters which control antagonistic motor responses.

Commissural connections mediate inhibition for the computation of interaural level difference in the barn owl

SummaryIn the barn owl (Tyto alba), the posterior nucleus of the ventral lateral lemniscus (VLVp) is the first site of binaural convergence in the pathway that processes interaural level difference (ILD), an important sound-localization cue. The neurons of VLVp are sensitive to ILD because of an excitatory input from the contralateral ear and an inhibitory input from the ipsilateral ear. A previously described projection from the contralateral cochlear nucleus, can account for the excitation. The present study addresses the source of the inhibitory input.We demonstrate with standard axonal transport methods that the left and right VLVps are interconnected via fibers of the commissure of Probst. We further show that the anesthetization of one VLVp renders ineffective the inhibition that is normally evoked by stimulation of the ipsilateral ear. Thus, one cochlear nucleus (driven by the ipsilateral ear) appears to provide inhibition to the ipsilateral VLVp by exciting commissurally-projecting inhibitory neurons in the contralateral VLVp.