Corticofugal modulation of the auditory thalamic reticular nucleus of the guinea pig

Neuronal responses to auditory stimuli and electrical stimulation were examined in 104 neurones in the auditory sector of thalamic reticular nucleus (TRN) and nine medial geniculate (MGB) neurones from anaesthetized guinea pigs. TRN neurones showed rhythmic spontaneous activities. TRN neurones changed firing pattern over time, from tonic to burst in a time interval of several seconds to tens of seconds. One-third of the TRN neurones (25/76) responded to the acoustic stimulus in a slow oscillation mode, either producing a spike burst at one time and responded with nothing another time, or producing a spike burst at one time and a single spike at the other. Thirty-two of 40 neurones received a corticofugal modulation effect. Nineteen of 32 neurones responded directly to electrical stimulation of the cortex with an oscillation of the same rhythm (7–14 Hz) as its auditory-evoked oscillation. Six neurones changed their firing pattern from burst to tonic when the auditory cortex was activated. As the TRN applied inhibition to the MGB, the oscillatory nature of inhibition would affect the fidelity of MGB relays. Thus, it was unlikely that the MGB was in relay mode when the TRN was in a slow oscillation mode. These results hint at a possible mechanism for the modulation of states of vigilance through the corticofugal pathway via the TRN.     

Time course of cortically induced fos expression in auditory thalamus and midbrain after bilateral cochlear ablation

Expression of c-fos in the medial geniculate body (MGB) and the inferior colliculus (IC) in response to bicuculline-induced corticofugal activation was examined in rats at different time points after bilateral cochlear ablation (4 h−30 days). Corticofugal activation was crucial in eliciting Fos expression in the MGB after cochlear ablation. The pars ovoidea (OV) of the medial geniculate body ventral division (MGv) showed dense Fos expression 4 h after cochlear ablation; the expression declined to very low levels at 24 h and thereafter. In turn, strong Fos expression was found in the pars lateralis (LV) of the MGv 24 h after cochlear ablation and dropped dramatically at 14 days. The dorsal division of the MGB (MGd) showed high Fos expression 7 days after cochlear ablation, which persisted for a period of time. Using multi-electrode recordings, neuronal activity of different MGB subnuclei was found to correlate well with Fos expressions. The temporal changes in cortically activated Fos expression in different MGB subnuclei after bilateral cochlear ablation indicate differential denervation hypersensitivities of these MGB neurons and likely point to differential dependence of these nuclei on both auditory ascending and corticofugal descending inputs. After bilateral cochlear ablation, significant increases in Fos-positive neurons were detected unilaterally in all IC subnuclei, ipsilateral to the bicuculline injection.     

An electrophysiological study of neural pathways for corticofugally inhibited neurons in the central nucleus of the inferior colliculus of the big brown bat, Eptesicus fuscus

This electrophysiological study tests the hypothesis that one possible neural pathway for corticofugally inhibited neurons in the central nucleus of the inferior colliculus (ICc) of the big brown bat, Eptesicus fuscus, is mediated through excitatory projections from the auditory cortex (AC) to the external nucleus of the IC (ICx), which then sends inhibitory inputs to the ICc. This study shows that all neurons in the ICx are broadly tuned to stimulus frequency. Electrical stimulation in the AC typically increases the number of impulses, expands the auditory spatial response areas, and broadens the frequency tuning curves (FTCs) of neurons in the ICx. This corticofugal facilitation is mediated at least in part through NMDA receptors, since application of DL-2-amino-5-phosphonovaleric acid (APV), an antagonist for NMDA, decreases these response properties of neurons in the ICx. Electrical stimulation in the ICx typically decreases the number of impulses, reduces the auditory spatial response areas, and narrows the FTCs of neurons in the ICc. This inhibition is mediated at least in part through GABA_A receptors, since application of bicuculline, an antagonist for GABA, increases these response properties of neurons in the ICc. These data suggest that corticofugal facilitation of the ICx and the inhibition of the ICx to the ICc may be one of the polysynaptic pathways for corticofugal inhibition of neurons in the ICc. Possible functions of this polysynaptic pathway in acoustic orientation and signal processing are discussed. Electronic Publication     

Corticofugal modulation on both ON and OFF responses in the nonlemniscal auditory thalamus of the guinea pig

Corticofugal modulation on both ON and OFF responses in various nuclei in the medial geniculate body (MGB) was examined by locally activating the auditory cortex and looking for effects on the neuronal responses to acoustic stimuli. In contrast with a major corticofugal facilitatory effect on the ON neurons in the lemniscal nucleus of the MGB of the guinea pigs, of 132 ON neurons tested in three conditions with cortical activation through each of three implanted electrodes, the majority of the tested conditions (319/396) that were sampled from the nonlemniscal nuclei of the MGB received inhibitory modulation from the activated cortex. This inhibitory effect was >50% for 99 cases while the auditory cortex was activated. Most of the OFF and ON-OFF MGB neurons (44/54) showed a facilitatory effect of 111.4 +/- 99.9%, and three showed a small inhibitory effect of 25.7 +/- 5.8% on their OFF responses. Thirty neurons in the border region between the lemniscal and nonlemniscal MGB showed mainly facilitatory corticofugal effects on both ON and OFF responses. Meanwhile, cortical stimulation induced almost exclusive inhibitory effects on the ON response and facilitatory effects on the OFF response in the MGcm. It is suggested that the OFF response is produced as a disinhibition from the inhibitory input of the auditory stimulus. The present results provide a possible explanation for selective gating of the auditory information through the lemniscal MGB while switching off other unwanted sensory signals and the interference from the limbic system, leaving the other auditory cortex prepared to process only the auditory signal.     

Inhibitory interactions in neuronal networks including cells of the auditory cortex and the medial geniculate body

The use of the method of cross-correlation analysis has made it possible to identify some specific features of inhibition in neuronal networks including cells from various loci of the auditory cortex (AC) and the medial geniculate body (MGB). It was demonstrated that inhibitory MGB (AC) neurons possess “convergent” properties which are manifested in the fact that one neuron simultaneously excites cells located in various loci of the AC and MGB, and “divergent” properties which are manifested in the fact that one and the same neuron may simultaneously inhibit neighboring cells and neurons from one or several AC (MGB) loci. There are short-axon inhibitory neurons in the AC which selectively act on the activity of one neighboring cell. An inhibitory AC neuron may be simultaneously included in the circuit of afferent and backward inhibition. Reciprocal connections between inhibitory MGB neurons were found. Simultaneous afferent inhibition of remote AC cells may lead to synchronization of their activity. The results make it possible to explain deviations from the principle of tonotopic organization in the AC and MGB. Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 44, No. 6, pp. 1046–1058, November–December, 1994.     

Modulatory effect of cortical activation on the lemniscal auditory thalamus of the Guinea pig

In the present study, we investigated the point-to-point modulatory effects from the auditory cortex to the thalamus in the guinea pig. Corticofugal modulation on thalamic neurons was studied by electrical activation of the auditory cortex. The modulation effect was sampled along the frontal or sagittal planes of the auditory thalamus, focusing on the ventral division (MGv) of the medial geniculate body (MGB). Electrical activation was targeted at the anterior and dorsocaudal auditory fields, to which the MGv projects and from which it assumptively receives reciprocal projections. Of the 101 MGv neurons examined by activation of the auditory cortex through passing pulse trains of 100-200 microA current into one after another of the three implanted electrodes (101 neurons x 3 stimulation sites = 303 cases), 208 cases showed a facilitatory effect, 85 showed no effect, and only 10 cases (7 neurons) showed an inhibitory effect. Among the cases of facilitation, 63 cases showed a facilitatory effect >100%, and 145 cases showed a facilitatory effect from 20-100%. The corticofugal modulatory effect on the MGv of the guinea pig showed a widespread, strong facilitatory effect and very little inhibitory effect. The MGv neurons showed the greatest facilitations to stimulation by the cortical sites, with the closest correspondence in BF. Six of seven neurons showed an elevation of the rate-frequency functions when the auditory cortex was activated. The comparative results of the corticofugal modulatory effects on the MGv of the guinea pig and the cat, together with anatomical findings, hint that the strong facilitatory effect is generated through the strong corticothalamic direct connection and that the weak inhibitory effect might be mainly generated via the interneurons of the MGv. The temporal firing pattern of neuronal response to auditory stimulus was also modulated by cortical stimulation. The mean first-spike latency increased significantly from 15.7 +/- 5.3 ms with only noise-burst stimulus to 18.3 +/- 4.9 ms (n = 5, P < 0.01, paired t-test), while the auditory cortex was activated with a train of 10 pulses. Taking these results together with those of previous experiments conducted on the cat, we speculate that the relatively weaker inhibitory effect compared with that in the cat could be due to the smaller number of interneurons in the guinea pig MGB. The corticofugal modulation of the firing pattern of the thalamic neurons might enable single neurons to encode more auditory information using not only the firing rate but also the firing pattern.     

Plasticity of bat's central auditory system evoked by focal electric stimulation of auditory and/or somatosensory cortices

Recent findings indicate that the corticofugal system would play an important role in cortical plasticity as well as collicular plasticity. To understand the role of the corticofugal system in plasticity, therefore, we studied the amount and the time course of plasticity in the inferior colliculus (IC) and auditory cortex (AC) evoked by focal electrical stimulation of the AC and also the effect of electrical stimulation of the somatosensory cortex on the plasticity evoked by the stimulation of the AC. In adult big brown bats (Eptesicus fuscus), we made the following major findings. 1) Electric stimulation of the AC evokes best frequency (BF) shifts, i.e., shifts in frequency-response curves of collicular and cortical neurons. These BF shifts start to occur within 2 min, reach a maximum (or plateau) at 30 min, and then recover approximately 180 min after a 30-min-long stimulus session. When the stimulus session is lengthened from 30 to 90 min, the plateau lasts approximately 60 min, but BF shifts recover approximately 180 min after the session. 2) The electric stimulation of the somatosensory cortex delivered immediately after that of the AC, as in fear conditioning, evokes a dramatic lengthening of the recovery period of the cortical BF shifts but not that of the collicular BF shift. The electric stimulation of the somatosensory cortex delivered before that of the AC, as in backward conditioning, has no effect on the collicular and cortical BF shifts. 3) Electric stimulation of the AC evokes BF shifts not only in the ipsilateral IC and AC but also in the contralateral IC and AC. BF shifts are smaller in amount and shorter in recovery time for contralateral collicular and cortical neurons than for ipsilateral ones. Our findings support the hypothesis that the AC and the corticofugal system have an intrinsic mechanism for reorganization of the IC and AC, that the reorganization is highly specific to a value of an acoustic parameter (frequency), and that the reorganization is augmented by excitation of nonauditory sensory cortex that makes the acoustic stimulus behaviorally relevant to the animal through associative learning.     

Spatial representation of corticofugal input in the inferior colliculus: a multicontact silicon probe approach

The inferior colliculus (IC) is a well-established target of descending projections from the auditory cortex (AC). However, our understanding of these pathways has been limited by an incomplete picture of their functional influence within the three-dimensional space of the IC. Our goal was to study the properties and spatial representation of corticofugal input in the IC of guinea pigs with a high degree of spatial resolution. We systematically mapped neural activity in the IC using two types of silicon substrate probes that allow for simultaneous recording at multiple neural sites. One probe provided a high resolution in the dorsal-ventral plane and the other provided spatial resolution in the medial-lateral plane. Electrical stimulation of the ipsilateral AC produced excitatory responses in the IC with thresholds usually below 5–10 µA. First spike latencies were predominantly in the 6–20 ms range, although latencies from 3–5 ms were also observed. Broadly distributed unimodal spike patterns with modal latencies greater than 30 ms were occasionally seen. The excitatory responses to cortical stimulation were mostly unimodal and occasionally bimodal with a wide range of spike distribution patterns and response durations. Excitation was often followed by suppression of spontaneous activity. Suppression of acoustic responses was observed even when there was little or no response to electrical stimulation, suggesting spatial-temporal integration. A few of the responding neurons showed purely inhibitory responses to electrical stimulation, suggesting that there are disynaptic routes of corticocollicular inhibition. Detailed spatial mapping revealed that the response patterns and their durations had a characteristic spatial distribution in the IC.     

Excitatory interactions in neuronal networks which include cells of the auditory cortex and the medial geniculate body

The use of the method of cross-correlation analysis to elucidate the interactions between simulatneously recorded neurons from various loci of the auditory cortex (AC) and the medial geniculate body (MGB) has made it possible to identify the following characteristics of the functional organization of the excitatory interactions in the thalamocortical neuronal networks: the interdependant impulse action of neurons located at various loci of the AC and MGB was determined by reciprocal excitatory connections; the efficiency of the connections between neurons of the AC, 400–500 μm apart, and between tonotopically associated neurons of the AC and MGB was approximately identical (associations were identified in 12% of the cases); the “divergent” properties of the MGB (AC) neurons were manifested in the fact that one and same neuron could simultaneously excite both neighboring cells and neurons from one or several loci of the AC (MGB); the “convergent” properties of the AC and MGB neurons were manifested in the fact that cells located at various loci of the AC and MGB simultaneously excited one neuron. The results make it possible to explain the deviations observed in the investigation of RF of neurons of the AC and MGB from the principle of tonotopical organization. It is hypothesized that the character of the organization of the excitatory connections in the thalamocortical networks may promote the creation of the necessary conditions for the modification of the efficiency of synapses between all of the elements of the network during the stimulation of individual elements. Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 44, No. 4-5, pp. 762–776, July–October, 1994.     

Cells in the rat auditory system have sensory-delay correlates during the performance of an auditory working memory task

Single unit activity was recorded from rat auditory cortex (AC), medial geniculate body (MGB), and inferior colliculus (IC) during performance of a continuous nonmatching-to-sample task. The rats made go and no-go responses to indicate whether the current tone was the same as (match) or different from (nonmatch) the preceding tone. Between 31% and 55% of the units from AC, MGB, and IC showed sensory correlates (differences in activity to the two types of tones), indicating an involvement in sensory discrimination. Twenty percent of the units from AC and MGB had delay correlates (sustained differential activity during the delay immediately after the tones), indicating an involvement in retention. Most of the units with delay correlates also had sensory correlates. These results suggest that the auditory system, especially AC and MGB, discriminates and retains auditory stimuli in an auditory working memory.     

Neural representations of temporally modulated signals in the auditory thalamus of awake primates

In sensory systems, the thalamus has historically been considered a relay station. Neural representations of temporal modulations in the auditory system undergo considerable changes as they pass from the inferior colliculus (IC) to the auditory cortex. We sought to determine in awake primates the extent to which auditory thalamic neurons contribute to these transformations. We tested the temporal processing capabilities of medial geniculate body (MGB) neurons in awake marmoset monkeys using repetitive click stimuli. MGB neurons were able to synchronize to periodic clicks at repetition rates significantly higher than auditory cortex neurons. Unlike responses in the MGB of anesthetized animals, >40% of MGB neurons in awake marmosets displayed nonsynchronized discharges when stimulated by high click rates (short interclick intervals). Such nonsynchronized MGB responses typically occurred at higher repetition rates than those observed in auditory cortex. In contrast to auditory cortex neurons, many MGB neurons exhibited both synchronized and nonsynchronized discharge patterns. In both MGB and auditory cortex, synchronized and nonsynchronized responses represented complementary ranges of interclick intervals (1/click rate). Furthermore, the temporal processing abilities of some MGB neurons were sensitive to the spectrotemporal parameters of the click stimuli used. Together, these findings suggest that MGB neurons participate in active transformations of the neural representations of temporal modulations from IC to auditory cortex. In particular, the MGB appears to be the first station in the auditory ascending pathway in which substantial nonsynchronized responses emerge.     

Plastic reorgaizations of the receptive fields of neurons of the auditory cortex and the medial geniculate body induced by microstimulation of the auditory cortex

The receptive fields of neurons (RFs) whose activity was simultaneously recorded at several loci of the auditory cortex (AC) and in the medial, geniculate body (MGB) were investigated before and after intracortical microstimulation (ICMS). Three types of neurons of the AC and MGB were distinguished on the basis of the character of the RFs: mono-, bi-, and polymodal. The RFs of the neighboring neurons in the AC (or in the MGB) could differ, while the RFs of remote neurons of the AC could be similar. The microstimulation of the AC could lead to changes in the RFs of neurons in the, stimulated locus and neighboring loci of the AC, as well as in the loci of the MGB tonotopically associated with them. It is hypothesized that long-term modification of the efficiency of synaptic transmission between different elements of the cortex-thalamus-cortex circuit which arises as the result of the circulation of impulses along this chain during ICMS may be the mechanism underlying the observed changes in the RFs of AC and MGB neurons. Institute of Higher Nervous Activity, Russian Academy of Sciences, Moscow. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 44, No. 3, pp. 548–568, May–June, 1994     

Structural changes in the adult rat auditory system induced by brief postnatal noise exposure

In previous studies (Grécová et al., Eur J Neurosci 29:1921–1930, 2009; Bures et al., Eur J Neurosci 32:155–164, 2010), we demonstrated that after an early postnatal short noise exposure (8 min 125 dB, day 14) changes in the frequency tuning curves as well as changes in the coding of sound intensity are present in the inferior colliculus (IC) of adult rats. In this study, we analyze on the basis of the Golgi–Cox method the morphology of neurons in the IC, the medial geniculate body (MGB) and the auditory cortex (AC) of 3-month-old Long–Evans rats exposed to identical noise at postnatal day 14 and compare the results to littermate controls. In rats exposed to noise as pups, the mean total length of the neuronal tree was found to be larger in the external cortex and the central nucleus of the IC and in the ventral division of the MGB. In addition, the numerical density of dendritic spines was decreased on the branches of neurons in the ventral division of the MGB in noise-exposed animals. In the AC, the mean total length of the apical dendritic segments of pyramidal neurons was significantly shorter in noise-exposed rats, however, only slight differences with respect to controls were observed in the length of basal dendrites of pyramidal cells as well as in the neuronal trees of AC non-pyramidal neurons. The numerical density of dendritic spines on the branches of pyramidal AC neurons was lower in exposed rats than in controls. These findings demonstrate that early postnatal short noise exposure can induce permanent changes in the development of neurons in the central auditory system, which apparently represent morphological correlates of functional plasticity.     

Augmentation of plasticity of the central auditory system by the basal forebrain and/or somatosensory cortex

Auditory conditioning (associative learning) or focal electric stimulation of the primary auditory cortex (AC) evokes reorganization (plasticity) of the cochleotopic (frequency) map of the inferior colliculus (IC) as well as that of the AC. The reorganization results from shifts in the best frequencies (BFs) and frequency-tuning curves of single neurons. Since the importance of the cholinergic basal forebrain for cortical plasticity and the importance of the somatosensory cortex and the corticofugal auditory system for collicular and cortical plasticity have been demonstrated, Gao and Suga proposed a hypothesis that states that the AC and corticofugal system play an important role in evoking auditory collicular and cortical plasticity and that auditory and somatosensory signals from the cerebral cortex to the basal forebrain play an important role in augmenting collicular and cortical plasticity. To test their hypothesis, we studied whether the amount and the duration of plasticity of both collicular and cortical neurons evoked by electric stimulation of the AC or by acoustic stimulation were increased by electric stimulation of the basal forebrain and/or the somatosensory cortex. In adult big brown bats (Eptesicus fuscus), we made the following major findings. 1) Collicular and cortical plasticity evoked by electric stimulation of the AC is augmented by electric stimulation of the basal forebrain. The amount of augmentation is larger for cortical plasticity than for collicular plasticity. 2) Collicular and cortical plasticity evoked by AC stimulation is augmented by somatosensory cortical stimulation mimicking fear conditioning. The amount of augmentation is larger for cortical plasticity than for collicular plasticity. 3) Collicular and cortical plasticity evoked by both AC and basal forebrain stimulations is further augmented by somatosensory cortical stimulation. 4) A lesion of the basal forebrain tends to reduce collicular and cortical plasticity evoked by AC stimulation. The reduction is small and statistically insignificant for collicular plasticity but significant for cortical plasticity. 5) The lesion of the basal forebrain eliminates the augmentation of collicular and cortical plasticity that otherwise would be evoked by somatosensory cortical stimulation. 6) Collicular and cortical plasticity evoked by repetitive acoustic stimuli is augmented by basal forebrain and/or somatosensory cortical stimulation. However, the lesion of the basal forebrain eliminates the augmentation of collicular and cortical plasticity that otherwise would be evoked by somatosensory cortical stimulation. These findings support the hypothesis proposed by Gao and Suga.     

Synaptic excitation in the dorsal nucleus of the lateral lemniscus

The dorsal nucleus of the lateral lemniscus (DNLL) is a distinct auditory neuronal group located ventral to the inferior colliculus (IC). It receives excitatory and inhibitory afferent inputs from various structures of the auditory lower brainstem and sends GABAergic inhibitory efferents mainly to the contralateral DNLL and the bilateral IC. The synaptic excitation in DNLL neurons consists of two components, an early fast depolarization and a later long lasting one. Glutamate is the probable excitatory neurotransmitter for DNLL neurons. alpha-Amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors mediate the early part of the excitation while N-Methyl-D-aspartate (NMDA) receptors mediate the long lasting component. The long lasting NMDA receptor-mediated component in the DNLL may contribute to a prolonged inhibition in the IC. The DNLL is thought to be a structure for processing binaural information. Most DNLL neurons in rat and bat are sensitive to interaural intensity differences (IIDs). They are excited by stimulation of the contralateral ear and inhibited by stimulation of the ipsilateral ear, showing an excitatory/inhibitory (EI) binaural response pattern. The EI pattern can be attributed to synaptic inputs that originate from various structures in the lower auditory brainstem and impinge on the DNLL neurons. In cat some DNLL neurons are sensitive to IIDs and some are sensitive to interaural time differences. In addition, DNLL neurons exhibit different temporal response patterns to contralateral tonal stimulation and respond to amplitude modulated tones, implying that DNLL may contribute to processing temporally complex acoustic information. DNLL neurons shape binaural responses in the contralateral inferior colliculus and auditory cortex through their inhibitory brainstem projections and contribute to the accuracy with which animals localize sounds in space.     

Arborization of corticothalamic axons in the auditory thalamus of the cat: a PHA-L tracing study

As a result of Phaseolus vulgaris leucoagglutinin (PHA-L) injection in the primary auditory cortex of the cat, portions of corticofugal axons could be traced individually in the reticular complex of the thalamus (RE) and in the medial geniculate body (MGB). On their way to the MGB, axons were seen to give off collaterals which terminated in RE. In the MGB, an individual corticofugal axon was fully reconstructed. It ramified at 3 distinct frontal levels in the rostral half of the pars lateralis (LV). Its terminal branches gave rise to boutons en passant and terminaux in a stripe of LV (parallel to the isofrequency contours), overlapping a cluster of retrogradely labeled neurons, supporting at the microscopic level the principle of the reciprocity of thalamocortical and corticothalamic projections.     

Modulation of cochlear hair cells by the auditory cortex in the mustached bat.

The corticofugal (descending) auditory system forms multiple feedback loops, and adjusts and improves auditory signal processing in the subcortical auditory nuclei. However, the mechanism by which the corticofugal system modulates cochlear hair cells has been unexplored. We found that electric stimulation of cortical neurons via the corticofugal system modulates cochlear hair cells in a highly specific way according to the relationship in terms of best frequency between cortical neurons and hair cells. Such frequency-specific effects can be explained by selective corticofugal modulation of individual olivocochlear efferent fibers.     

Corticofugal modulation of the paradoxical latency shifts of inferior collicular neurons

The central auditory system creates various types of neurons tuned to different acoustic parameters other than a specific frequency. The response latency of auditory neurons typically shortens with an increase in stimulus intensity. However, approximately 10% of collicular neurons of the little brown bat show a "paradoxical latency-shift (PLS)": long latencies to intense sounds but short latencies to weak sounds. These neurons presumably are involved in the processing of target distance information carried by a pair of an intense biosonar pulse and its weak echo. Our current studies show that collicular PLS neurons of the big brown bat are modulated by the corticofugal (descending) system. Electric stimulation of cortical auditory neurons evoked two types of changes in the PLS neurons, depending on the relationship in the best frequency (BF) between the stimulated cortical and recorded collicular neurons. When the BF was matched between them, the cortical stimulation did not shift the BFs of the collicular neurons and shortened their response latencies at intense sounds so that the PLS became smaller. When the BF was unmatched, however, the cortical stimulation shifted the BFs of the collicular neurons and lengthened their response latencies at intense sounds, so that the PLS became larger. Cortical electric stimulation also modulated the response latencies of non-PLS neurons. It produced an inhibitory frequency tuning curve or curves. Our findings indicate that corticofugal feedback is involved in shaping the spectrotemporal patterns of responses of subcortical auditory neurons presumably through inhibition.     

Regulation of inhibitory synapses by presynaptic D₄ dopamine receptors in thalamus

Dopamine (DA) receptors are the principal targets of drugs used in the treatment of schizophrenia. Among the five DA receptor subtypes, the D(4) subtype is of particular interest because of the relatively high affinity of the atypical neuropleptic clozapine for D(4) compared with D(2) receptors. GABA-containing neurons in the thalamic reticular nucleus (TRN) and globus pallidus (GP) express D(4) receptors. TRN neurons receive GABAergic afferents from globus pallidus (GP), substantia nigra pars reticulata (SNr), and basal forebrain as well as neighboring TRN neuron collaterals. In addition, TRN receives dopaminergic innervations from substantia nigra pars compacta (SNc); however, the role of D(4) receptors in neuronal signaling at inhibitory synapses is unknown. Using whole cell recordings from in vitro pallido-thalamic slices, we demonstrate that DA selectively suppresses GABA(A) receptor-mediated inhibitory postsynaptic currents (IPSCs) evoked by GP stimulation. The D(2)-like receptor (D(2,3,4)) agonist, quinpirole, and selective D(4) receptor agonist, PD168077, mimicked the actions of DA. The suppressive actions of DA and its agonists were associated with alterations in paired pulse ratio and a decrease in the frequency of miniature IPSCs, suggesting a presynaptic site of action. GABA(A) receptor agonist, muscimol, induced postsynaptic currents in TRN neurons were unaltered by DA or quinpirole, consistent with the presynaptic site of action. Finally, DA agonists did not alter intra-TRN inhibitory signaling. Our data demonstrate that the activation of presynaptic D(4) receptors regulates GABA release from GP efferents but not TRN collaterals. This novel and selective action of D(4) receptor activation on GP-mediated inhibition may provide insight to potential functional significance of atypical antipsychotic agents. These findings suggest a potential heightened TRN neuron activity in certain neurological conditions, such as schizophrenia and attention deficit hyperactive disorders.     

Antidromic activation reveals tonotopically organized projections from primary auditory cortex to the central nucleus of the inferior colliculus in guinea pig

The inferior colliculus (IC) is highly modulated by descending projections from higher auditory and nonauditory centers. Traditionally, corticofugal fibers were believed to project mainly to the extralemniscal IC regions. However, there is some anatomical evidence suggesting that a substantial number of fibers from the primary auditory cortex (A1) project into the IC central nucleus (ICC) and appear to be tonotopically organized. In this study, we used antidromic stimulation combined with other electrophysiological techniques to further investigate the spatial organization of descending fibers from A1 to the ICC in ketamine-anesthetized guinea pigs. Based on our findings, corticofugal fibers originate predominantly from layer V of A1, are amply scattered throughout the ICC and only project to ICC neurons with a similar best frequency (BF). This strict tonotopic pattern suggests that these corticofugal projections are involved with modulating spectral features of sound. Along the isofrequency dimension of the ICC, there appears to be some differences in projection patterns that depend on BF region and possibly isofrequency location within A1 and may be indicative of different descending coding strategies. Furthermore, the success of the antidromic stimulation method in our study demonstrates that it can be used to investigate some of the functional properties associated with corticofugal projections to the ICC as well as to other regions (e.g., medial geniculate body, cochlear nucleus). Such a method can address some of the limitations with current anatomical techniques for studying the auditory corticofugal system.