Muscimol suppression of the dorsal cochlear nucleus modifies frequency tuning in rats

The cochlear nucleus is composed of three sub-nuclei: the dorsal (DCN), anteroventral (AVCN) and posteroventral cochlear nucleus (PVCN). Intrinsic connections from the DCN to the AVCN are inhibitory and organised tonotopically. In this investigation, this pathway and its possible role in frequency tuning was examined using in vivo extracellular recordings. Extracellular recordings were made from 191 units in the AVCN, 69 of which were recorded after suppression of DCN by application of the GABA agonist Muscimol (15 ng, 0.26 mM). Tuning curves were plotted and characteristic frequency (CF) and response threshold (measured in dB SPL) were determined for each unit. Units recorded post-Muscimol showed significantly broader tuning characteristics and lower thresholds. Primary-like and transient chopper neurons contributed to this decrease in threshold suggesting that they receive ‘on' CF inhibitory drive from the DCN. Sustained chopper units did not show a significant decrease in response threshold after Muscimol; however, there was a tendency for broader tuning and a significant increase in CF tone evoked maximum discharge rate and chopping frequency suggesting that the DCN may play a role in regulating the temporal firing of these units in addition to providing lateral inhibition. These results suggest that the DCN to AVCN pathway may aid in fine tuning frequency information.     

Reduced spontaneous activity in the dorsal cochlear nucleus of Scn8a mutant mice

Spontaneous activity was recorded in the dorsal cochlear nucleus of brain slices from mice homozygous for the med-J and jolting mutations in the neuronal sodium channel alpha-subunit Scn8a. Densities of spontaneously active neurons in slices from both mutants were significantly lower than in control slices. Spontaneous firing patterns with bursts of action potentials were recorded from approximately 50% of the neurons in control slices, but the typical bursting patterns were not observed in neurons of med-J and jolting mouse slices. The results suggest that this voltage-gated sodium channel is essential for the spontaneous bursting firing of cochlear nucleus cartwheel neurons. This mutant animal model may be useful for the study of the functional roles of cochlear nucleus neurons.     

Blast‐Induced tinnitus and spontaneous firing changes in the rat dorsal cochlear nucleus

Exposure to high‐pressure blast shock waves is known to cause tinnitus. Although the underlying mechanisms may involve damage to structures in the ear and/or direct brain impact, which triggers a cascade of neuroplastic changes in both auditory and nonauditory centers, it remains unclear how the induced neuroplasticity manifests neurophysiologically. This study investigates the influence of blast exposure on spontaneous firing rates (SFRs) in the dorsal cochlear nucleus (DCN) and its time course in rats with blast‐induced tinnitus. Each rat was exposed to a single blast at 22 psi. Behavioral evidence of tinnitus was measured by using a gap‐detection acoustic startle–reflex paradigm. SFRs were measured 1 day, 1 month, and 3 months after blast exposure. The results showed that nine rats with blast‐induced tinnitus and hearing loss developed hyperactivity immediately and that the induced hyperactivity persisted in six rats with tinnitus at 1 month after blast exposure. At 3 months after blast exposure, however, the induced hyperactivity of four rats with tinnitus transitioned to hypoactivity. In addition, the 20–30‐kHz, and >30‐kHz regions in the DCN of rats with and without blast‐induced tinnitus were more affected than other frequency regions at different recovery time points after blast exposure. These results demonstrate that the neural mechanisms underlying blast‐induced tinnitus are substantially different from those underlying noise‐induced tinnitus. © 2014 Wiley Periodicals, Inc.     

The dorsal cochlear nucleus of the adult Lurcher mouse is specifically invaded by embryonic grafted Purkinje cells

The fate of embryonic Purkinje cells grafted over the brainstem surface of the adult Lurcher mouse was analyzed using anti-calbindin (CaBP) immunocytochemistry. Purkinje cells are able to migrate specifically into the molecular layer of the host dorsal cochlear nucleus (DCoN) and develop dendritic trees that are practically isoplanar, suggesting synaptic interactions with the parallel fibres of the DCoN. These results provide a new argument in favour of the homology between the cerebellum and the DCoN.     

Subcellular localization of the inositol 1,4,5-triphosphate receptor, P400, in the vestibular complex and dorsal cochlear nucleus of the rat

The subcellular localization of the inositol 1,4,5-trisphosphate receptor protein, P₄₀₀, was studied in the vestibular complex, an area to which Purkinje cells project, as well as in neurons of the dorsal cochlear nucleus and in ectopic Purkinje cells of adult rat brain. The receptor was demonstrated by electron microscopical immunocytochemistry using the avidin-biotin peroxidase complex procedure, with the monoclonal antibody 4C11 raised against mouse cerebellar inositol 1,4,5-trisphosphate receptor protein. Immunoreactivity was found in preterminal fibres and terminal boutons in the nuclei of the vestibular complex, generally associated with the subsurface systems and stacks or fragments of smooth endoplasmic reticulum. Ectopic Purkinje cells and cartwheel cells of the dorsal cochlear nucleus also displayed immunoreactivity, but this was much less intense in the latter. The results of the present study suggest that this receptor protein, involved in the release of Ca²⁺, is located in sites that enable it to influence the synthesis, transport and release of neurotransmitters.     

Modulatory effects of somatosensory electrical stimulation on neural activity of the dorsal cochlear nucleus of hamsters

The effects of somatosensory electrical stimulation on the dorsal cochlear nucleus (DCN) activity of control and tone-exposed hamsters were investigated. One to three weeks after sound exposure and control treatment, multiunit activity was recorded at the surface of the left DCN before, during, and after electrical stimulation of the basal part of the left pinna. The results demonstrated that sound exposure induced hyperactivity in the DCN. In response to electrical stimulation, neural activity in the DCN of both control and exposed animals manifested four response types: S-S, suppression occurring during and after stimulation; E-S, excitation occurring during stimulation and suppression after; S-E, suppression occurring during stimulation and excitation after; and E-E, excitation occurring during and after stimulation. The results showed that there was a higher incidence of suppressive (up to 70%) than of excitatory responses during and after stimulation in both groups. In addition, there was a significantly higher degree of suppression after, rather than during stimulation. At high levels of electrical current, the degree of the induced suppression was generally higher during and after stimulation in exposed animals than in controls. The similarity of our results to those of previous clinical studies further supports the view that DCN hyperactivity is a direct neural correlate of tinnitus and that somatosensory electrical stimulation can be used to modulate DCN hyperactivity. Optimization of stimulation strategy through activating only certain neural pathways and applying appropriate stimulation parameters may allow somatosensory electrical stimulation to be used as an effective tool for tinnitus suppression.     

Development of the cochlear innervation of the dorsal cochlear nucleus of the hamster

The development of cochlear fibers and terminals in the dorsal cochlear nucleus of the hamster was studied with light and electron microscopic techniques. Like the dorsal cochlear nucleus of most other mammals, the dorsal cochlear nucleus of the adult hamster is a laminated structure. Three distinct layers can be identified in cresyl-violet-stained sections: the molecular layer, the fusiform cell layer, and the deep layer. The deep layer consists of a superficial zone, free of large cell bodies, and a deep zone which contains the somas of giant cells. Horseradish peroxidase and degeneration studies reveal that the cochlear fibers ramify throughout the deep and fusiform cell layers of the adult hamster but do not enter the molecular layer. In the electron microscope, three types of terminals that contact the fusiform and the giant cells can be distinguished. Only one type of terminal (type LR) degenerates after cochlear ablation and is, therefore, thought to be of cochlear origin. Type LR terminals are found throughout the deep and fusiform cell layers and contact the somas of giant and fusiform cells, as well as their intermingled dendrites in the deep layer. In Golgi-impregnated material, cochlear fibers are not found in the dorsal cochlear nucleus of the neonatal hamster, although they have entered the ventral cochlear nucleus. Ingrowth of cochlear fibers into the dorsal cochlear nucleus occurs over the first postnatal week and one-half. A spatial gradient is evident during the ingrowth of the fibers in that they invade the dorsomedial parts of the dorsal cochlear nucleus before they invade the ventrolateral parts. In all parts of the nucleus, the fibers enter the deepest layer and grow progressively more superficially. In the electron microscope, the first appearance of type LR terminals at each depth lags behind the ingrowth of the fibers by about two days. In hamsters, fibers from the basal turns of the cochlea terminate in the dorsomedial dorsal cochlear nucleus, while fibers from the apical turns terminate in the ventrolateral dorsal cochlear nucleus (DCN). The dorsomedial to ventrolateral gradient in the ingrowth of the cochlear fibers into the DCN indicates that the fibers from the basal turn are the first to arrive. Several components of the mammalian cochlea have been shown to mature at the base of the cochlea before they mature at the apex. The present study suggests that maturation gradients in the cochlear nucleus parallel those observed in the cochlea.     

Strychnine alters the fusiform cell output from the dorsal cochlear nucleus

Anatomical and physiological evidence suggests that fusiform cells, the major output neurons of the dorsal cochlear nucleus (DCN), receive significant inhibitory input. Fusiform cells often display strongly non-monotonic rate-intensity functions and pauser-buildup or buildup tone-evoked temporal responses, patterns which may be mediated by inhibitory neurotransmitters. Other neurons located within the fusiform cell layer or in the more superficial molecular layer display varied rate-intensity functions and temporal responses. Neurons displaying response properties characteristic of fusiform cells are sensitive to iontophoretic application of the inhibitory amino acid neurotransmitter, glycine. Application of the glycine receptor antagonist, strychnine, alters the non-monotonic portion of the rate-intensity function at doses which do not alter spontaneous activity or near-threshold tone-evoked responses. These neurons are also sensitive to GABA and the GABAB agonist, (-)-baclofen, but are insensitive to the GABAA antagonist, bicuculline. DCN neurons which display monotonic rate-intensity functions and temporal response properties different than those associated with fusiform cells are sensitive to bicuculline, (-)-baclofen, and GABA. These data suggest that a glycinergic input onto fusiform cells may control the non-monotonic nature of the response of these neurons near characteristic frequency and therefore may contribute significantly to the nature of the output of the DCN.     

Protein kinase C mediates potentiation of synaptic transmission by phorbol ester at parallel fibers in the dorsal cochlear nucleus

Many cells in the outer two layers of the dorsal cochlear nucleus (DCN) express high levels of the phospholipid-activated, calcium dependent kinase, protein kinase C (PKC), an enzyme that can phosphorylate numerous proteins involved in neurotransmission and postsynaptic signaling. We investigated the effects of stimulating PKC with phorbol esters (phorbol 12-13 diacetate; PDAc) on parallel fiber synaptic transmission in brain slices of the guinea pig DCN. Phorbol esters increased the amplitude of the postsynaptic components of the field potential, including the excitatory post-synaptic field potential (fEPSP) and the population spike following electric stimulation of parallel fibers. Phorbol esters simultaneously decreased paired-pulse facilitation, suggesting that transmitter release mechanisms were affected. Potentiation of synaptic transmission and diminished paired-pulse potentiation were also observed in intracellular recordings of DCN neurons. The effects of phorbol esters were antagonized by the specific PKC blockers bisindolylmaleimide and calphostin C. Although modulation of the synaptic potentials appears to be mediated by presynaptic PKC, the differential effects of PDAc on the fEPSP and the population spike also suggest the involvement of postsynaptic PKC and postsynaptic targets. These experiments demonstrate that protein kinase C is capable of profoundly modulating synaptic transmission at parallel fiber synapses in the DCN.     

The neuronal types and the distribution of 5-hydroxytryptamine and enkephalin-like immunoreactive fibers in the dorsal cochlear nucleus of the North American opossum

The opossum dorsal cochlear nucleus is divided into four layers distinguishable either on the basis of differential distribution of neuron types or by neuropil organization. We have used Nissl, Golgi and protargol stained preparations to examine these components. Four types of neurons (excluding granule cells) are seen. The principal neurons have large cell bodies arranged in a sheet defining layer II, their apical dendrites extend dorsally to form an elaborate arbor in layer I and their basal dendrites pass ventrally into layer III. Round cells are found throughout layers I and II. Their densely packed dendritic domains feature thick spine encrusted dendrites that have many recurrent branches. Giant neurons have large perikarya scattered throughout layers III and IV and long thick dendrites that radiate throughout the nucleus. Small multipolar neurons (stellate cells) are found throughout the nucleus. The more superficial ones have small perikarya whereas those found in deeper layers tend to be large. All four layers of the nucleus may be clearly differentiated in protargol stained sections. Layer I has small, thin fibers in parallel array, layer II has a mixture of fibers with an apparent random orientation, layer III has large diameter vertically oriented fibers, and layer IV has fibers of similar diameter but deposed horizontally. Immunohistochemical techniques have been used to identify specific fiber systems in the neuropil of the dorsal cochlear nucleus. Fibers containing 5-hydroxytryptamine (5-HT) immunoreactivity were prevalent in layers I, III and IV but sparse in layer II. Fibers containing enkephalin (ENK)-immunoreactivity were prevalent in layer I and II with only a few scattered fibers in the deeper layers. Isolated clusters of 5-HT and ENK immunoreactive fibers in layer II were found around principal neuron somata; similar clusters in the deep layers were located around the somata of giant neurons. The wide distribution of 5-HT immunoreactive fibers suggests they may be involved in a general regulation of activity in this nucleus; conversely the more circumscribed distribution of ENK immunoreactive fibers would suggest a restricted involvement of this fiber system with a specific feature of information processing.     

Locus coeruleus-induced inhibition of dorsal cochlear nucleus neurons in comparison with lateral vestibular nucleus neurons

The effects of conditioning stimulation of the locis coeruleus (LC) on the neuron activity of dorsal cochlear nucleus (DCN), which is rich in noradrenergic nerve terminals, were compared with those on the lateral vestibular nucleus (LVN), devoid of such terminals, to determine whether or not noradrenaline is responsible for the LC-induced inhibition. The conditioning stimuli applied to the LC had no effect on either the field potential or the spike generation of mono- and polysynaptic neurons in the LVN elicited by VIIIth cranial nerve stimulation. In contrast, the spike firing of the DCN neurons with VIIIth cranial nerve stimulation was significantly inhibited by LC conditioning stimulation. The inhibition of spike generation was mainly observed in the DCN neurons which fired spikes with a longer latency. The inhibition of DCN neurons by LC conditioning stimulation did not occur in the cats pretreated with reserpine; however, a rapid recovery of the inhibition was produced by intraventricular application of noradrenaline. These results are in good agreement with the histochemical findings and support our previous conclusion that noradrenaline acts as an inhibitory transmitter or modulator on the nuclei where noradrenergic nerve terminals derived from the LC are located. In addition, the vestibular input in the primary relay nucleus is apparently not regulated by noradrenaline originating in the LC.     

Cartwheel neurons of the dorsal cochlear nucleus: a Golgi-electron microscopic study in rat

Cartwheel neurons in rat dorsal cochlear nucleus (DCN) were studied by Golgi impregnation-electron microscopy. Usually situated in layers 1-2, cartwheel neurons (10-14 micrometers in mean cell body diameter) have dendritic trees predominantly in layer 1. The dendrites branch at wide angles. Most primary dendrites are short, nontapering, and bear only a few sessile spines. Secondary and tertiary dendrites are short, curved, and spine-laden. The perikaryon forms symmetric synapses with at least two kinds of boutons containing pleomorphic vesicles. The euchromatic nucleus is indented and has an eccentric nucleolus. The cytoplasm shows several small Nissl bodies, a conspicuous Golgi apparatus, and numerous subsurface and cytoplasmic cisterns of endoplasmic reticulum with a narrow lumen, joined by mitochondria in single or multiple assemblies. In primary dendrites mitochondria are situated peripherally, while in distal branches they become ubiquitous and relatively more numerous. Dendritic shafts usually form symmetric synapses with boutons that contain pleomorphic vesicles. The majority of the dendritic spines are provided with a vesiculo-saccular spine apparatus. All dendritic spines have asymmetric synapses. Most of these are formed with varicosities of thin, unmyelinated fibers (presumably axons of granule cells) running parallel to the long axis of the DCN or radially. These varicosities contain round, clear synaptic vesicles. On the initial axon segment few symmetric synapses are present. The axon acquires a thin myelin sheath after a short trajectory. Cartwheel neurons outnumber all other neurons in layers 1-2 (with the exception of granule cells), and presumably correspond to type C cells with thinly myelinated axons described by Lorente de Nó. The axons of these neurons provide a dense plexus in the superficial layers without leaving the DCN. The possible functional role of cartwheel neurons is discussed.     

Targets, receptors and effects of muscarinic neuromodulation on giant neurones of the rat dorsal cochlear nucleus

Although cholinergic modulation of the cochlear nucleus (CN) is functionally important, neither its cellular consequences nor the types of receptors conveying it are precisely known. The aim of this work was to characterise the cholinergic effects on giant cells of the CN, using electrophysiology and quantitative polymerase chain reaction. Application of the cholinergic agonist carbachol increased the spontaneous activity of the giant cells; which was partly the consequence of the reduction in a K⁺ conductance. This effect was mediated via M4 and M3 receptors. Cholinergic modulation also affected the synaptic transmission targeting the giant cells. Excitatory synaptic currents evoked by the stimulation of the superficial and deep regions of the CN were sensitive to cholinergic modulation: the amplitude of the first postsynaptic current was reduced, and the short-term depression was also altered. These changes were mediated via M3 receptors alone and via the combination of M4, M2 and M3 receptors, when the superficial and deep layers, respectively, were activated. Inhibitory synaptic currents evoked from the superficial layer showed short-term depression, but they were unaffected by carbachol. In contrast, inhibitory currents triggered by the activation of the deep parts exhibited no significant short-term depression, but they were highly sensitive to cholinergic activation, which was mediated via M3 receptors. Our results indicate that pre- and postsynaptic muscarinic receptors mediate cholinergic modulation on giant cells. The present findings shed light on the cellular mechanisms of a tonic cholinergic modulation in the CN, which may become particularly important in evoking contralateral excitatory responses under certain pathological conditions.     

Afferent and efferent innervation patterns of the cochlear nucleus (dorsal medullary nucleus) of the leopard frog

The afferent and efferent innervation patterns of the frog dorsal medullary nucleus (DMN; anuran homolog of the cochlear nucleus) were examined by studying the anterograde and retrograde transport patterns of horseradish peroxidase injected focally into the nucleus. It was found that this structure projected bilaterally to the superior olivary nuclei (SON) and dorsal midbrain tegmental nuclei, and contralaterally to the opposite DMN, the lateral lemniscus nucleus (LLN) and the torus semicircularis (TS). The termination sites in the TS were restricted to the laminar and principal nuclei. The DMN in turn received projections from these structures with the exception of the TS and dorsal tegmental nuclei. The projection to the ipsilateral LLN and TS was not pronounced. In addition to the above findings, the ascending projection to the DMN, SON and TS, as well as the centrifugal projection from the SON, were found to be organized tonotopically.     

Purkinje-like cells in the cochlear nucleus of the Common Tree Shrew (Tupaia glis) identified by calbindin immunohistochemistry

The dorsal cochlear nucleus (DCN) of Tree Shrews (Tupaia glis; n=2) was examined by calbindin (CB) immunohistochemistry for the presence of Purkinje-like cells (PLCs), detected previously in only four different mammals. We found up to eight CB-immunoreactive PLCs in the left and right DCN, and a few axons, likely of PLC origin, that appeared to leave the DCN. These findings suggest that PLCs may have a wider distribution through mammalian species, and may represent more than just misrouted cells.     

Changes in the tonotopic map of the dorsal cochlear nucleus in hamsters with hair cell loss and radial nerve bundle degeneration

Hamsters were exposed to an intense tone (10 kHz) at levels and durations sufficient to cause hair cell loss and radial nerve bundle degeneration. A previous study reported changes in the tonotopic map of the dorsal cochlear nucleus (DCN) in hamsters with tone-induced stereocilia loss. Such changes appear similar to those observed by others in the auditory nerve following acoustic trauma, and suggest that the map alterations have a peripheral origin. However, the potential for tonotopic map reorganization after more severe lesions involving cellular degeneration in the cochlea has not yet been determined. The purpose of the present study was to determine how the tonotopic map of the DCN appears in animals with severe cochlear injury involving hair cell loss and radial nerve bundle degeneration. Neural population thresholds and tonotopic organization were mapped over the surface of the DCN in normal unexposed animals and those showing tone-induced lesions. The results indicate that cochlear lesions characterized mainly by radial bundle degeneration in a restricted portion of the organ of Corti cause changes in a corresponding region of the tonotopic map which reflect primarily changes in the shape and thresholds of neural tuning curves. In many cases the center of the lesion was represented in the DCN as a distinct characteristic frequency (CF) gap in the tonotopic map in which responses were either extremely weak or absent. In almost all cases the map area representing the center of the lesion was bordered by an expanded region of near-constant CF, a feature superficially suggestive of map reorganization (i.e., plasticity). However, these expanded map areas had abnormal tip thresholds and showed other features suggesting that their CFs had been shifted downward by distortion and deterioration of their original tips. Such changes in neural tuning following tone-induced loss of anatomical input to the central auditory pathway are similar to those observed in our previous study and by others in the auditory nerve following less severe acoustic trauma, and thus would seem to have a peripheral origin. Thus, changes in the DCN tonotopic map can be explained by peripheral modifications and do not seem to involve plastic changes (i.e., reorganization).     

Somatosensory inputs modify auditory spike timing in dorsal cochlear nucleus principal cells

In addition to auditory inputs, dorsal cochlear nucleus (DCN) pyramidal cells in the guinea pig receive and respond to somatosensory inputs and perform multisensory integration. DCN pyramidal cells respond to sounds with characteristic spike-timing patterns that are partially controlled by rapidly inactivating potassium conductances. Deactivating these conductances can modify both spike rate and spike timing of responses to sound. Somatosensory pathways are known to modify response rates to subsequent acoustic stimuli, but their effect on spike timing is unknown. Here, we demonstrate that preceding tonal stimulation with spinal trigeminal nucleus (Sp5) stimulation significantly alters the first spike latency, the first interspike interval and the average discharge regularity of firing evoked by the tone. These effects occur whether the neuron is excited or inhibited by Sp5 stimulation alone. Our results demonstrate that multisensory integration in DCN alters spike-timing representations of acoustic stimuli in pyramidal cells. These changes likely occur through synaptic modulation of intrinsic excitability or synaptic inhibition.     

Effect of light on the acetylcholine concentrations of the suprachiasmatic nucleus in the rat

Acetylcholine concentrations were determined in suprachiasmatic nucleus of rats sacrificed by irradiation of microwave, using radioimmunoassay. No significant rhythmicity was observed over a 24-h period in rats blinded for two weeks. When the light was given at 22.00 h (illumination schedule L:07.00-19.00 h) in intact rats, acetylcholine concentration increased 30 and 60 min after light on in suprachiasmatic nucleus, but not in the other control site. These results suggest that endogenous circadian rhythm of acetylcholine concentration is absent in suprachiasmatic nucleus, but light may affect acetylcholine concentration of this site.     

Trauma-specific insults to the cochlear nucleus in the rat

The effect of acoustic overstimulation on the neuronal number of the cochlear nucleus (CN) was investigated by using unbiased stereological methods in rats. We found that, after 9 weeks of recovery, neurons in the anteroventral cochlear nucleus (AVCN) degenerated, whereas those in the posteroventral and dorsal cochlear nuclei (PVCN and DCN) were preserved. The noise trauma induced near complete loss of the outer hair cells throughout the cochlea, and the inner hair cells were preserved only in the more apical regions. This pattern of selective loss of AVCN neurons in this study was different from trauma induced by auditory deafferentation by mechanical compression of auditory neurons. In contrast to noise trauma, mechanical compression caused loss of neurons in the PVCN and DCN. After 5 weeks of recovery from mechanical compression, there was no loss of inner or outer hair cells. These findings indicate that auditory deprivation, induced by different experimental manipulations, can have strikingly different consequences for the central auditory system. We hypothesized that AVCN neuronal death was induced by excitotoxic mechanisms via AMPA‐type glutamate receptors and that excitatory neuronal circuits developed after acoustic overstimulation protected the PVCN and DCN against neuronal death. The results of the present study demonstrate that hearing loss from different etiologies will cause different patterns of neuronal degeneration in the CN. These findings are important for enhancing the performance of cochlear implants and auditory brainstem implants, because diverse types of hearing loss can selectively affect neuronal degeneration of the CN. © 2012 Wiley Periodicals, Inc.     

Effects of various frequency electrical stimulation of the dorsal raphe nucleus on spontaneous firing activities in the rat subthalamic nucleus★

BACKGROUND： Some investigations have demonstrated that exogenous 5-hydroxytryptamine increases the spontaneous firing rate of subthalamic nucleus （STN） neurons in the rat brain. OBJECTIVE： To validate the effect of electrical stimulation to the dorsal raphe nucleus （DRN） on the neuronal activities of the STN in rats, as well as analyze the differences in the effects of electrical stimulation at various frequencies. DESIGN, TIME AND SETTING： Experiments were performed from March 2007 to June 2007 in the Electrophysiology Laboratory of Liaoning Medical University with a randomized controlled animal study design. MATERIALS： Twenty-four healthy male Sprague-Dawley （SD） rats, weighing 250-350 g, were selected for this study. An A320R constant electrical stimulator was purchased from World Precision Instruments Company （USA）; a Spike 2 biological signal acquisition system was purchased from British CED Company. METHODS： Twenty-four SD rats were randomly assigned into a model group and a normal group, with 12 rats in each group. To mimic Parkinson＇s disease, rats in the model group were injected with 4μL of 6-hydroxydopamine into the right striatum, then received deep brain stimulation. Rats in the normal group received deep brain stimulation in same brain region without modeling. Electrical stimulation （width, 0.06 ms; intensity, 0.2-0.6 mA; frequency, 20-130 Hz; train duration, 5 seconds） was delivered to the DRN. MAIN OUTCOME MEASURES： The firing rates of STN neurons were observed by extracellular recording using a biological signal acquisition system. RESULTS： DRN-high-frequency stimulation （DRN-HFS） induced excitation in 59% of the STN neurons in the normal group and 50% of the STN neurons in the model group; mean firing rates increased significantly from （7.14±0.75） and （7.94 ± 0.61） Hz to （11.17 ±1.49） and （12.11 ± 1.05） Hz, respectively （P 〈 0.01）. Spontaneous firing rate increased significantly in 53% of neurons in normal rats in a frequency-dep