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R L Hyson

Publications and source records attributed to R L Hyson.

At least 19 recordsLinked to original sources

Activation of metabotropic glutamate receptors is necessary for transneuronal regulation of ribosomes in chick auditory neurons.

Elimination of auditory nerve activity results in atrophy and death of nucleus magnocellularis (NM) neurons in the chick. One early event in the degeneration of NM neurons is a disruption of their ribosomes. This experiment examines the role of metabotropic glutamate receptors in afferent regulation of ribosomes. The auditory nerve on one side of a chick brainstem slice was stimulated in vitro. Rapid stimulation-dependent changes in ribosomes were visualized by immunolabeling using an antibody, called Y10B, that recognizes ribosomal RNA. In normal media, NM neurons on the stimulated side of the slice show greater Y10B labeling than the unstimulated NM neurons on the opposite side of the same slice. The role of metabotropic glutamate receptors was evaluated by unilaterally stimulating the auditory nerve in media containing the metabotropic glutamate receptor antagonist (RS)-alpha-methyl-4-carboxyphenyl-glycine (MCPG). Addition of MCPG to the bath did not block EPSPs produced by stimulating the auditory nerve. However, MCPG did prevent the stimulation-dependent regulation of ribosomes in NM neurons (as indexed by Y10B labeling). These data suggest that glutamate may play a trophic role in the young auditory system through activation of metabotropic glutamate receptors.

2-Amino-5-phosphonovalerate↗

Effect of GABA on the processing of interaural time differences in nucleus laminaris neurons in the chick.

Neurons in the avian nucleus laminaris (NL) are the first to receive binaural information and are presumed to play a role in encoding interaural time differences (ITD). NL not only receives excitatory projections from the ipsi- and contralateral nucleus magnocellularis, but also receives inhibitory (GABAergic) input. This study investigates how GABA (gamma-aminobutyric acid) influences ITD coding in NL. Intracellular responses of chick NL neurons were studied in a brain slice preparation. Both excitatory inputs to NL were electrically activated and the delay between trains of bilateral stimuli (simulated-interaural time difference [s-ITD]) was varied. The resulting s-ITD functions were recorded in the presence of 0-75 microM GABA. The discharge rate of NL neurons varied with s-ITD. Cells responded maximally using s-ITDs at which the peak of the ipsi- and contralateral excitatory postsynaptic potentials occurred simultaneously (favourable s-ITD). At unfavourable s-ITDs, the discharge rates usually fell below unilateral levels. GABA had contrary effects on the s-ITD functions depending on the drug concentration. A low GABA dose enhanced excitability at favourable s-ITD, but not at unfavourable s-ITDs. In contrast, higher GABA concentrations diminished excitability. Moderate GABA concentrations had no consistent effect. These results suggest that the GABAergic input to NL will either increase or decrease the excitability of the NL neuron depending on the degree to which this GABAergic input is activated. A gain control hypothesis is presented in which the GABAergic input makes ITD processing in NL independent of the stimulus intensity by adjusting the excitability of NL neurons.

Animals↗

Transneuronal regulation of ribosomes after blockade of ionotropic excitatory amino acid receptors.

Elimination of auditory nerve activity results in death and atrophy of neurons in the cochlear nucleus, nucleus magnocellularis (NM), of the chick. One early event believed to lead to cell death and atrophy is the disruption of ribosomes in the NM neuron. A useful assay for visualizing these ribosomal changes is immunolabeling with the antibody Y10B, which recognizes ribosomal RNA. Activity-dependent changes in Y10B labeling have been observed both in vivo, after unilateral cochlea removal and in vitro after unilateral auditory nerve stimulation. Although it is clear that activity is crucial for maintaining ribosomal integrity, the identity of the important transynaptic signal(s) is not known. It is possible that this trophic signal is glutamate, the neurotransmitter release from the auditory nerve. The present study investigates the role of ionotropic glutamate receptors in the activity-dependent regulation of ribosomes, as measured by the Y10B immunoreactivity. Brain slices containing the auditory nerve and NM on both sides were obtained from hatchling chicks. The auditory nerve on one side of the slice was stimulated for 1 h. The slice was then processed for Y10B immunoreactivity. As expected, greater Y10B immunolabeling was observed on the stimulated side of the slice. Unexpectedly, however, this immunolabeling difference was still observed after blocking NMDA receptors (50 microM DL-APV), non-NMDA receptors (20 microM CNQX), or blocking both ionotropic receptor subtypes (APV and CNQX). This was true even though CNQX eliminated driven postsynaptic potentials. These data suggest that ionotropic glutamate receptors are not necessary for the activity-dependent regulation of ribosomes in NM neurons.

Animals↗

Differences in expression of GABAA receptor subunits, but not benzodiazepine binding, in the chick brainstem auditory system.

Neurons in nucleus magnocellularis (NM) and nucleus laminaris (NL) of the chick brainstem auditory system show an unusual physiological response to GABA. Examination of these nuclei using in situ hybridization for GABAA receptor subunits showed a differential expression of the gamma 2 and alpha 1 subunits. The gamma 2 subunit was found in both NM and NL, but the alpha 1 subunit was found in NL only. Like NL, other areas of the tissue section that showed labeling with the gamma 2 probe, such as the medial vestibular nucleus (VeM) and granule cells of the cerebellum (CB), also labeled with the alpha 1 probe. Thus, given that NM labeled with the gamma 2 probe, the absence of the alpha 1 subunit was unusual in this tissue. This difference in subunit composition suggests that there may also be a difference in GABA receptor function in NM compared to these neighboring areas. One feature of the GABAA receptor believed to be related to the presence of gamma 2 and alpha 1 subunits is specific pharmacological properties of the benzodiazepine modulatory site. It has been proposed that the alpha 1 subunit is necessary for producing a GABAA receptor with a benzodiazepine site that has Type I binding characteristics. The present experiments challenge this hypothesis. Based on the differential presence of the alpha 1 subunit, one would expect that GABA receptors in NM would show different benzodiazepine binding properties than NL, VeM, and CB. However, displacement of 3H-flunitrazepam binding using CL 218,872, which differentiates between the Type I and Type II receptors, showed no difference between these areas. Additionally, the relatively high affinity for CL 218,872 suggests that even NM contains Type I receptors.

Animals↗

A depolarizing inhibitory response to GABA in brainstem auditory neurons of the chick.

Neurons in the brainstem auditory nuclei, n. magnocellularis and n. laminaris, of the chick are contacted by terminals containing the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). In this report we describe the physiological response of these neurons to GABA using an in vitro slice preparation. In brainstem auditory neurons, GABA produced a depolarization of up to 20 mV and an associated decrease in input resistance. This depolarization was inhibitory; action potentials generated by orthodromic synaptic drive, antidromic stimulation and intracellular current injection were prevented by GABA application. The GABA response still occurred when synaptic transmission was prevented by perfusing the slice with a medium containing low Ca2+ and high Mg2+ concentrations. Thus, the effects of GABA were directly on the postsynaptic neuron and not via an interneuron. Whole-cell voltage clamp of neurons revealed that the reversal potential of the inward current was approximately -45 mV, suggesting that the channel responsible for this response is not selective for Cl- or K+. Pharmacological analyses suggest that this GABA receptor has properties distinct from those typical of either GABAa or GABAb receptors. Although a similar response was observed with the GABAa agonist, muscimol, it was not blocked by the GABAa antagonist, bicuculline. The response was not evoked by the GABAb agonist, baclofen, and was not blocked by the GABAb antagonist phaclofen. This unusual depolarizing response is not a common feature of all brainstem neurons. Neurons located in the neighboring medial vestibular nucleus show a more traditional response to GABA application. At resting potential, these neurons show a hyperpolarizing or biphasic response associated with a decrease in input resistance and inhibition of their spontaneous activity. GABA-induced responses in the medial vestibular nucleus are blocked by bicuculline. These results suggest that an unusual form of the GABA receptor is present in the brainstem auditory system of the chick. It is possible that this form of GABA receptor provides an efficient mechanism for inhibiting the relatively powerful EPSPs received by brainstem auditory neurons, or it may play a trophic role in the afferent regulation of neuronal integrity in this system.

Animals↗

Activity-dependent regulation of a ribosomal RNA epitope in the chick cochlear nucleus.

Elimination of auditory nerve activity results in rapid metabolic changes, cell atrophy, and cell death in nucleus magnocellularis (NM), the cochlear nucleus of the chick. The transneuronal signals involved in the activity-dependent regulation of NM neurons are not well understood. One of the most rapid transneuronal effects is alteration in protein synthesis by NM neurons. Previous studies using an in vitro preparation of the brain stem auditory system suggested that up-regulation of protein synthesis in NM neurons requires the action of some trophic substance released by active auditory nerve fibers. Here, similar results were obtained when measuring changes in immunoreactivity using a monoclonal antibody (Y10B) that recognizes ribosomal RNA. This immunolabeling assay has advantages over the global protein synthesis assay in that it is not sensitive to possible changes in specific activity of the precursor pool or possible differences in the uptake of the labeled amino acids. Unilateral stimulation of the auditory nerve for 1 h resulted in greater immunolabeling of NM neurons on the stimulated side of the slice. This is consistent with previous in vivo results after unilateral deafferentation. Blockade of synaptic transmission by maintaining the slice in a low-Ca2+/high Mg2+ medium prevented the stimulation-induced difference in immunolabeling. Electrical stimulation of the postsynaptic NM neurons alone (antidromic stimulation, via electrical stimulation of NM neuron axons) did not result in greater immunolabeling. Rather, antidromically stimulated neurons tended to show lighter labeling. Thus, the transneuronal regulation of ribosomes in NM neurons appears to require some substance released from the active auditory nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Glutamate-stimulated phosphatidylinositol metabolism in the avian cochlear nucleus.

This study examined the ability of the excitatory amino acid glutamate and its analogs to stimulate phosphatidylinositol metabolism in isolated cochlear nucleus tissue from young chicks. In the presence of lithium chloride, glutamate and (+/-)-1-aminocyclopentyl-trans-1,3-dicarboxylate (ACPD) stimulated the formation of inositol phosphates to levels significantly above unstimulated control levels. Unexpectedly, quisqualate did not stimulate inositol phosphates formation. The N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate (APV), the ionotropic kainate/quisqualate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and the putative metabotropic glutamate receptor antagonist 2-amino-3-phosphonopropionate (AP3) had no effect on the glutamate stimulated formation of inositol phosphates. We conclude that a metabotropic glutamate receptor is present on cochlear nucleus neurons of posthatch chicks and is able to stimulate formation of inositol phosphates.

2-Amino-5-phosphonovalerate↗

Cochlear microphonic measurements of interaural time differences in the chick.

The major cues for the sound localization are the interaural differences in the timing and intensity of acoustic information. This poses a difficult coding problem for animals with relatively small heads, such as birds, because interaural time differences (ITDs) would have a small range and magnitude and interaural intensity differences (IIDs) would be significant for only high frequency sounds. It has been suggested that this coding problem is mitigated in birds by an enhancement of ITDs and IIDs resulting from the acoustic coupling of the two middle ear cavities through an interaural canal. In this report, the functional ITDs for sounds at different azimuthal locations were recorded in young chicks, and the contribution of middle ear acoustic coupling was evaluated. ITDs were calculated from simultaneous cochlear microphonic (CM) recordings evoked by pure tone stimuli. These effective ITDs were larger than predicted by the physical separation of the two ears, and this enhancement was more pronounced at low (0.8 and 1 kHz) than at high (2 and 4 kHz) frequencies, reaching maximum values of approximately 180 and 100 microseconds, respectively. The amplitude of the CM also varied as a function of sound source location. This variation was as much as +/- 30%, even for the low frequency tones. This suggests that IID cues are also available to the chick. To determine the contribution of middle ear acoustic coupling to the timing and amplitude of the CM response, the CM in one ear was measured prior to, and following occlusion of the contralateral external auditory canal. The cochlear microphonic from the ear distal to the sound source advanced in time and increased in amplitude when the ear proximal to the sound source was sealed. These effects were more pronounced for low frequency sounds. These findings confirm that acoustic coupling of the middle ear cavities plays a role in enhancing sound localization cues in the chick.

Acoustic Stimulation↗

The astrocytic response to afferent activity blockade in chick nucleus magnocellularis is independent of synaptic activation, age, and neuronal survival.

Astrocytes in nucleus magnocellularis (NM) of the chick respond to afferent activity blockade with increased immunoreactivity for glial fibrillary acidic protein (GFAP). NM neurons respond to the same manipulations with reduced protein synthesis, ribosomal dissociation, and subsequent death of a subset of these neurons. In the present study, we sought to evaluate the relationship between these neuronal and glial responses and to determine if similar activity-dependent mechanisms mediate them. We first examined the anatomical relationship between NM neurons and astrocytic processes by electron microscopy and GFAP immunostaining. Both methods showed that NM neurons deprived of activity for 6 hr were apposed by more glial processes than active NM neurons. However, we found no preferential positioning of GFAP-immunoreactive processes near neurons of the dying or surviving populations, and there were no differences in glial process apposition to dying versus surviving neurons at the EM level. To determine whether the astrocytic response is similar to the neuronal response in age dependence, GFAP immunoreactivity was analyzed in adult chickens following unilateral afferent activity blockade. Unlike the neuronal response to activity blockade, the astrocytic response is equally strong in adult animals. These results imply an independence of the neuronal and astrocytic responses to activity blockade, raising the possibility that these two cell types may be responding to different activity-related signals. This possibility was tested using an in vitro slice preparation. Unilateral stimulation of NM was provided in three ways: orthodromically, antidromically, and orthodromically in a low-calcium medium. The regulation of astrocytic GFAP immunoreactivity by these manipulations of activity was then analyzed. The results of these experiments show that, unlike neuronal protein synthesis, astrocytic GFAP immunoreactivity can be suppressed by either presynaptic or postsynaptic neuronal activity. Therefore, the astrocytes and neurons are regulated by different activity-dependent signals and, by the present measures, their responses to activity blockade appear independent of one another.

Aging↗

Coincidence detection by binaural neurons in the chick brain stem.

1. Neurons in nucleus laminaris (NL) of birds are the first to receive binaural information and are presumed to play a role in encoding interaural time differences (ITDs). We studied extracellular single-unit responses of NL neurons in slices of the auditory brain stem of the chick. The afferents to NL were activated by electrical stimulation of nucleus magnocellularis (NM) or the auditory nerve. Changes in responses were measured as the delay between trains of bilateral stimuli (the simulated interaural time difference or S-ITD, n = 26) was varied and as the interstimulus interval and stimulus amplitude were varied (n = 61). 2. The probability of an action potential and the action-potential latency varied as a function of interstimulus interval. Most NL neurons showed a greater response probability and a shorter response latency to an interstimulus interval between 2.5 and 3.5 ms. The interstimulus interval that produced the minimum response latency was slightly longer than the interval that produced the maximum response probability. In contrast, NM neurons (n = 4) showed no preferred rate, instead, the probability of firing increased as the interstimulus interval increased. 3. Responses to bilateral stimulation showed that NL neurons can act as coincidence detectors. NL neurons responded most reliably when activated simultaneously by their two inputs and, at favorable S-ITDs, two subthreshold inputs combined to produce an action potential. 4. NL neurons also exhibited inhibition during bilateral stimulation. At unfavorable S-ITDs a subthreshold input combined with a suprathreshold input produced fewer action potentials than evoked by the suprathreshold input alone. 5. The latency of the bilateral response varied as a function of S-ITD. At S-ITDs near coincidence the latency of the bilateral response was shorter than the latency of either of the unilateral responses. Away from coincidence, the latency of the bilateral response was largely determined by the latency of the stronger unilateral response. When the unilateral responses were of similar strength, the earlier stimulus determined the latency of the bilateral response. 6. The range of S-ITDs producing a maximal response varied as a function of stimulus strength but was never less than approximately 300 microseconds. This is greater than the maximum possible ITD of sound calculated for the chick's head size. From these data we hypothesize that, in the chick, single units cannot uniquely encode ITDs, but rather ITDs may be coded by the proportion of maximally firing cells along an isofrequency band in NL.

Animals↗

Projections from the lateral nucleus of the trapezoid body to the medial superior olivary nucleus in the gerbil.

We made small injections of horseradish peroxidase into the medial superior olivary nucleus (MSO) of gerbils in order to examine the sources of input into that nucleus. As previously described, the MSO receives inputs from neurons in the rostral part of both anteroventral cochlear nuclei. In addition, we found evidence for a projection from the ipsilateral lateral nucleus of the trapezoid body (LNTB). Our results are also compatible with previous reports that the medical nucleus of the trapezoid body (NMTB) projects to the MSO. It is likely that these projections into the MSO from the LNTB and MNTB are sources of inhibitory synaptic inputs.

Animals↗

A circuit for coding interaural time differences in the chick brainstem.

Third-order auditory neurons in the avian nucleus laminaris (NL) are the first to receive binaural input. In the chick, NL consists of a monolayer of neurons with polarized dendritic arbors oriented dorsally and ventrally. Afferents from second-order neurons in the ipsilateral nucleus magnocellularis (NM) innervate the dorsal dendrites of NL neurons, distributing processes of approximately equal length to NL neurons along an isofrequency band (roughly caudomedial to rostrolateral). Afferents from the contralateral NM innervate the ventral dendrites of NL neurons, distributing collateral branches sequentially as they proceed from caudomedial to rostrolateral along the isofrequency band of neurons. This innervation pattern could be the basis of a "delay line" circuit, as postulated in models of neural networks mediating sound localization. We examined this circuit by analyzing evoked field potentials using a brain slice preparation containing both NL and NM. The results were consistent with the previous anatomical findings. When the ipsilateral auditory nerve or ipsilateral NM was stimulated, there was no consistent variation in the latency of postsynaptic field potentials across the medial-to-lateral extent of NL. In contrast, when the contralateral NM or NM axons in the crossed dorsal cochlear tract were stimulated, a linear increase in the latency of postsynaptic potentials was observed from medial to lateral positions in NL. When stimulation amplitudes for both the ipsilateral and contralateral inputs were adjusted so as to produce little or no postsynaptic field potential, simultaneous bilateral stimulation evoked a pronounced response. Thus, NL neurons can act as "coincidence detectors." The amplitude of the postsynaptic response was dependent on the relative timing of stimulation of the two inputs. The optimal time difference changed systematically across the medial-to-lateral extent of NL. This system of delay lines and coincidence detectors could provide a mechanism for converting interaural time differences into a "place map" within NL.

Animals↗

Afferent regulation of neurons in the brain stem auditory system.

We have reviewed a series of experiments which begin to examine the cellular events underlying afferent regulation of neuronal structure. Our initial interest in such experiments stemmed from a desire to understand the cellular nature of experiential influences on brain development. While this remains a long-range goal, it's elusive nature has become increasingly apparent; how will we know when such a goal is achieved? On the other hand, it has become increasingly clear that by approaching this question as a subset of the larger problem of tissue interactions regulating nervous system structure and function, some progress is possible. In this respect, understanding afferent regulation is part and parcel of understanding "competition." Both exemplify the fact that we are dealing with a dynamic system, where changes in the balance of extracellular factors result in a cascade of events defining a new "steady state." Unfortunately, most of our methods are limited to taking "snap-shots" of a few parameters and attempting to reconstruct an epic. Our analyses of the postsynaptic events following cochlea removal have only scratched the surface. They are beginning to reveal myriad cellular processes that are dramatically altered by changing the balance of synaptic activity, or "synaptic drive," in a neuronal system. We have been continually struck by the rapidity of these postsynaptic changes when the manipulations are performed on immature animals. While the kinetics of metabolic and structural events we have studied do not yet match those of ionic events involved in information transmission, the two classes of intercellular communication are coming much closer. Some neuromodulators can alter synaptic currents for up to many seconds, and we have shown that altering afferent activity can cause changes in protein synthesis within a few minutes. The merging of these two classes of phenomena should come as no surprise since our studies and many others have definitively linked a variety of metabolic and structural events to changes in the synaptic drive between two neurons. On the other hand, this progress does highlight the need for increased attention to the short-term changes following manipulations of afferent activity. Hopefully such studies will lead to an understanding of the intracellular chain of events responsible for the regulation of neuronal form. A second area of interest has been the age restrictions on the events we have studied.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Transneuronal regulation of protein synthesis in the brain-stem auditory system of the chick requires synaptic activation.

The cellular mechanisms by which afferents influence their target neurons were investigated using a slice preparation of the chick brain-stem auditory system. Each brain slice contained portions of the auditory nerve and the second-order auditory nucleus, nucleus magnocellularis (NM), bilaterally. NM neurons on one side of the slice were stimulated either orthodromically, via activation of the ipsilateral auditory nerve, or antidromically, via electrical stimulation of their axons. NM neurons on the other side of the slice were not stimulated and served as a within-animal control population. Evoked activity was monitored extracellularly in all preparations. Orthodromic activation of NM neurons for either 1.5 or 3.5 hr resulted in enhanced protein synthesis by these neurons. This result is similar to those of previous in vivo experiments (Steward and Rubel, 1985; Born and Rubel, 1988). When slices were maintained in a medium having low Ca2+ and high Mg2+ concentrations, both synaptic transmission from the auditory nerve to NM and also the difference in protein synthesis between the stimulated and unstimulated sides of the brain were blocked. Antidromic activation of NM neurons did not enhance protein synthesis, but rather resulted in reliably less synthesis by the stimulated cells. Together, these results suggest that activity-dependent release of some "trophic" substance from the auditory nerve is necessary for this form of transneuronal regulation. Electrical activity of the postsynaptic neuron per se is not sufficient for increasing protein synthesis in these cells.

Animals↗

Ontogenetic change in the analysis of sound frequency in the infant rat.

Previous research has shown that there is an ontogenetic shift in the spatial code of sound frequency in the cochlea and central auditory nuclei. During ontogenesis, a given area of the basilar membrane or central auditory nuclei is maximally stimulated by sounds of progressively higher frequencies. Here, a similar ontogenetic shift in the rat's "perception" of sound frequency is reported. Animals were trained with a tone (CS) paired with footshock (US) and generalization of their conditioned response (CR) to different frequencies was assessed either 0.5 or 72 hr later. When 15-day-old animals were trained with an 8-kHz tone and tested 0.5 hr later, greater suppression of activity (CR) was evoked by the 8-kHz tone than by either a 12-kHz or a 6-kHz tone. When tested 72 hr after training, however, greater suppression of activity was evoked by a 12-kHz tone than by the 8-kHz training stimulus or by a 24-kHz tone. This shift in the peak of the generalization gradient could not be accounted for by changes in unconditioned responses to the test stimuli. Additionally, the observed shift in the generalization gradient was age-dependent. It was not observed when pups were trained at 18 days old and tested 72 hr later. The implications of these data for studies of the ontogenesis of learning and memory are discussed.

Age Factors↗

Opiate and non-opiate analgesia induced by inescapable tail-shock: effects of dorsolateral funiculus lesions and decerebration.

Previous studies have demonstrated that inescapable tail-shock can produce either non-opiate or opiate short-term analgesia, dependent on the number of shocks delivered. Additionally, extended exposure to inescapable tail shock can produce long-term, opiate analgesic effects. Several lines of investigation suggest that the psychological dimension of perceived controllability may powerfully influence these phenomena in that each form of opiate analgesia can only be produced following exposure to inescapable, rather than equal amounts and distribution of escapable, shock. This has suggested that these opiate analgesias result from the organism's learning that it has no control over shock. Although it has been assumed that the opiate and non-opiate analgesias induced by tail shock may be subserved by neural circuitry similar to that mediating morphine analgesia and other forms of environmentally induced analgesia, no direct evidence exists to support this assumption. The present study sought to provide an initial attempt at defining the neural circuitry involved in these phenomena by examining the effect of bilateral dorsolateral funiculus (DLF) lesions and decerebration. These experiments revealed that pathways within the spinal cord DLF are critical for the production of short-term non-opiate analgesia, short-term opiate analgesia, and long-term opiate analgesia since bilateral DLF lesions abolished all three pain inhibitory effects. Additionally, it was found that decerebration did not attenuate either the short-term non-opiate or short-term opiate analgesia induced by inescapable tail shock. Combining the observations that these non-opiate and opiate short-term effects are not reduced by decerebration yet are abolished by DLF lesions clearly delimits the source of descending pain inhibition as being within the caudal brainstem.

Animals↗

Ontogenesis of learning: II. Variation in the rat's reflexive and learned responses to acoustic stimulation.

The ontogenesis of the rat's reflexive and simple learned reactions to acoustic stimulation was investigated in five experiments. The pattern of results suggests that (a) reflexive reactions to tonal stimulation emerge earlier in ontogenesis than the capacity to learn about these stimuli, and (b) the age at which simple Pavlovian conditioning is first observed depends on the nature of the acoustic conditioned stimulus (CS). Specifically, these data suggest that pups are not capable of simple Pavlovian conditioning to a 2000-Hz tone (CS) paired with an oral infusion of sucrose (US) until they are 14-15 days old. The same acoustic stimulus will, however, evoke reflexive reactions (startle inspiration) in pups as young as 10-12 days old. Additionally, when a different auditory stimulus (an intermittent train of clicks) serves as the CS, there is evidence of conditioning in pups only 12-13 days old. It is suggested that these age-related dissociations in the emergence of reflexive and simple learned responses to sound reflect a caudal-to-rostral maturational sequence of the components of the ascending auditory system.

Acoustic Stimulation↗

Ontogenesis of learning: III. Variation in the rat's differential reflexive and learned responses to sound frequencies.

The ontogenesis of the rat's differential response to variation in sound frequency was investigated. Two behavioral procedures were employed: (a) a differential Pavlovian conditioning procedure that provided a means of inferring the pup's capacity to learn to respond differentially on the basis of sound frequency (e.g., 2000 Hz vs 900 Hz), and (b) a habituation-generalization task that indexed the capacity to discriminate different sound frequencies from the pup's reflexive behavior. Pups less than 17 days old failed to learn to respond differentially to a 2000-Hz vs 900-Hz tone (Experiment I, IIA, IIB, and III). In contrast, pups only 14 days old discriminated tones that differed by as little as 200 Hz when the reflex-habituation-generalization procedure was employed (Experiment IV). This suggests that the reflexive and learned behaviors, potentially controlled by sound frequency, are dissociated during ontogenesis, the former emerging prior to the latter. These data were interpreted within a neurobiological framework that related ontogenetic changes in behavioral capacity to a caudal-to-rostral maturational sequence in the ascending auditory system of the components that contribute to these capacities.

Acoustic Stimulation↗