荷包牡丹碱和马钱子碱对小鼠皮层及下丘听神经元声反应潜伏期的影响

频率和强度是声音的两个重要参数,通常以听觉神经元动作电位发放频次编码这两个参数 . 研究表明,声反应潜伏期也可编码声音频率和强度,但尚不清楚潜伏期编码这两个参数究竟发生于哪一级听觉核团 . 如果声音参数由同级中枢编码,则这样的编码方式可能发生改变 . 反之,如果编码方式未发生变化,则意味着声音信息是由低位神经元编码的 . GABA 和甘氨酸 (Gly) 是听中枢普遍分布的抑制性递质 . 通过施加它们的拮抗剂荷包牡丹碱和马钱子碱,观测小鼠皮层和下丘听觉神经元声反应潜伏期的变化 . 结果表明,由反应潜伏期表征声音频率和强度的关系不因 GABA 和 Gly 作用的改变而发生变化,提示频率和强度与反应潜伏期之间的编码关系可能是由低位听神经元编码并向上传递的,而不是在同级中枢 ( 皮层或下丘 ) 完成的 .     

Effects of GABA-mediated inhibition on direction-dependent frequency tuning in the frog inferior colliculus

Earlier studies from our laboratory have shown that the frequency selectivity of neurons in the frog inferior colliculus is direction dependent. The goal of this study was to test the hypotheses that gamma-aminobutyric acid or GABA (but not glycine)-mediated synaptic inhibition was responsible for the direction-dependence in frequency tuning, and that GABA acted through creation of binaural inhibition. We performed single unit recordings and investigated the unit's free-field frequency tuning, and/or the unit's response to the interaural level differences (under dichotic stimulation), before and during local applications of antagonists specific to gamma-aminobutyric acid a and glycine receptors. Our results showed that application of bicuculline produced a broadening of free-field frequency tuning, and differential changes in free-field frequency tuning depending on sound direction, i.e., more pronounced at azimuths at which the unit exhibited narrower frequency tuning under the pre-drug condition, thereby typically abolishing direction dependence in tuning. Application of strychnine produced no change in frequency tuning. The results from dichotic stimulation further revealed that bicuculline typically elevated and/or flattened the unit's interaural-level-difference response function, indicating a reduction in the strength of binaural inhibition. Our study provides evidence that gamma-aminobutyric acid-mediated binaural inhibition is important for direction dependence in frequency tuning. Accepted: 24 July 1998     

Transmitters and pathways mediating inhibition of spinal itch-signaling neurons by scratching and other counterstimuli

Scratching relieves itch, but the underlying neural mechanisms are poorly understood. We presently investigated a role for the inhibitory neurotransmitters GABA and glycine in scratch-evoked inhibition of spinal itch-signaling neurons in a mouse model of chronic dry skin itch. Superficial dorsal horn neurons ipsilateral to hindpaw dry skin treatment exhibited a high level of spontaneous firing that was significantly attenuated by cutaneous scratching, pinch and noxious heat. Scratch-evoked inhibition was nearly abolished by spinal delivery of the glycine antagonist, strychnine, and was markedly attenuated by respective GABA(A) and GABA(B) antagonists bicuculline and saclofen. Scratch-evoked inhibition was also significantly attenuated (but not abolished) by interruption of the upper cervical spinal cord, indicating the involvement of both segmental and suprasegmental circuits that engage glycine- and GABA-mediated inhibition of spinal itch-signaling neurons by noxious counterstimuli.     

GABA介导杏仁外侧核对皮层A Ⅰ区神经元声反应的抑制:在体微电泳研究

在SD大鼠上应用多顺利完成微电极方法,观察微电泳CABA及其受体的拮抗剂或激动剂对杏仁外侧核（LA）抑制皮层AⅠ神经元声反应效应的影响。结果显示,电泳GABA能抑制皮层AⅠ区神经元的电活动,电泳GABAA受体拮抗剂bicuculline（BIC）则能易化其反应;电刺激LA能抑制皮层AⅠ区听神经元声反应,电泳GABA产生类拟于刺激LA的抑制效应;LA对皮层AⅠ区神经的抑制效应能被BIC所翻转,而不能被什氨酸受体拮抗剂strychnine所翻转,电泳GABAB型受体例激动剂baclofen对神经元声反应无影响。上术结果表明,GABA可能是介民LA抑制皮层AⅠ区神经元声反应的最终递质,并且是通过GABAA受体作用的。     

GABAergic inhibition shapes frequency tuning and modifies response properties in the superior olivary nucleus of the leopard frog

The role of gamma-aminobutyric acid (GABA)ergic inhibition in shaping the excitatory frequency tuning of 74 neurons in the superior olivary nucleus of the leopard frog, Rana pipiens, was studied using iontophoretic application of the GABA(A) receptor antagonist, bicuculline methiodide. For 37 neurons, bicuculline application broadened and/or changed the configuration of the excitatory frequency-tuning curve. Results indicate that GABA-mediated inhibition not only sharpens the tuning curves of neurons but also plays a critical role in creating new frequency tuning properties in the superior olivary nucleus. Bicuculline application affected other neuronal response properties as well. Spontaneous firing rate increased 11-338% for 18 of 59 neurons. For 32 of 58 neurons there was an increase in stimulus-evoked discharge rate and a change in rate-level function. There was no qualitative effect on the discharge pattern of 60 neurons, though 2 tonically responding neurons did show an increase (> 30%) in response duration. Additional roles for GABAergic inhibition in monaural signal analysis are discussed.     

Evidence that glycine and GABA mediate postsynaptic inhibition of bulbar respiratory neurons in the cat.

Experiments were carried out on decerebrate cats to identify transsynaptic mediators of spontaneous postsynaptic inhibition of bulbar inspiratory and postinspiratory neurons. Somatic membrane potentials were recorded through the central micropipette of a coaxial multibarreled electrode. Blockers of type A gamma-aminobutyric acid (GABA-A) and glycine receptors were iontophoresed extracellularly from peripheral micropipettes surrounding the central pipette. Effective antagonism was demonstrated by iontophoresis of agonists with antagonists; application of strychnine antagonized the action of glycine but not GABA, and application of bicuculline antagonized the action of GABA but not glycine. In both types of neurons, iontophoresis of either antagonist depolarized the somatic membrane and increased input resistance throughout the respiratory cycle. Bicuculline preferentially depolarized the somatic membrane in both types of neurons during inactive phases. Strychnine increased the firing rate of inspiratory neurons during inspiration despite maintenance of somatic membrane potential at preiontophoresis levels. Tetrodotoxin reduced the effects of iontophoresed bicuculline and strychnine, suggesting that the action of the antagonists required presynaptic axonal conduction. The present results suggest that presynaptic release of both GABA and glycine contributes to tonic postsynaptic inhibition of bulbar respiratory neurons. GABA-A receptors appear to contribute to inhibition during inactive phases in inspiratory and postinspiratory neurons, whereas glycinergic mechanisms appear to contribute to inspiratory inhibition in inspiratory neurons.     

Kinetic Analysis of Miniature Synaptic Currents in Rat Substantia Gelatinosa Neurons

Interneurons of the substantia gelatinosa (SG) form a complex synaptic network in the dorsal horn of the spinal cord. The properties of miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs, respectively) were studied in spinal cord slices of 3- to 4-week-old rats. The reversal potentials of the currents were close to 0 mV for excitatory and –70 mV for inhibitory events. Under recording conditions close to physiological ones (holding potential –40 mV, temperature 32°C, low intracellular [Cl^–]), the mean rise times of these currents were, respectively, 1.0 and 1.8 msec. The decay of the currents was monoexponential in the majority of occurrences (94 and 91.4%), with a time constant (τ) of 2.7 msec for mEPSCs and 7.2 msec for mIPSCs. A part (8.6%) of mIPSCs had an additional slow component with τ = 30.1 msec. All mEPSCs were blocked by 10 mM CNQX, an antagonist of the AMPA/kainate subtype of glutamate receptors. Monoexponential mIPSCs were blocked by 1 mM strychnine, an antagonist of glycine receptors, while two-component mIPSCs required the additional presence of 10 mM bicuculline, a blocker of GABAA receptors. Only two cells of 23 (~9%) demonstrated pure GABA-ergic mIPSCs (τ = 26.2 msec). It is concluded that, under physiological conditions, AMPA/kainate but not NMDA receptors mediate excitatory synaptic transmission in SG neurons. Synaptic inhibition is mediated predominantly by glycine receptors, with mild fractions of IPSCs provided by GABA-ergic transmission and GABA/glycine co-release.     

Cytology of large neurons in the guinea pig dorsal cochlear nucleus contacting the inferior colliculus

Large neurons in the dorsal cochlear nucleus of the guinea pig which project to the inferior colliculus were identified after injections of the neural tracer WGA-HRP. Retrograde labelled cells (pyramidal and giant neurons) in the dorsal cochlear nucleus were glycine and GABA immunonegative and showed a similar ultrastructure. Between 30 and 60% of their perimeter was covered by axo-somatic boutons, most of which (>50%) contained pleomorphic synaptic vesicles. Other boutons (about 40% of total) contained flat vesicles and few (5-6%) contained round vesicles, a characteristic of the excitatory cells innervating the inferior colliculus. Immunogold-cytochemistry, coupled to silver intensification, showed that more than 50% of axo-somatic pleomorphic boutons and over 90% of boutons containing flat and pleomorphic vesicles store glycine. Rare WGA-HRP labelled axo-somatic boutons containing flat-pleomorphic vesicles were seen on pyramidal and giant neurons. This suggests that a few inhibitory collicular terminals contact the excitatory large neurons in the dorsal cochlear nucleus.     

Interaction between glutamate and GABA systems in the integration of sympathetic outflow by the paraventricular nucleus of the hypothalamus

The paraventricular nucleus (PVN) of the hypothalamus is a central site known to modulate sympathetic outflow. Excitatory and inhibitory neurotransmitters within the PVN dictate final outflow. The goal of the present study was to examine the role of the interaction between the excitatory neurotransmitter glutamate and the inhibitory neurotransmitter GABA in the regulation of sympathetic activity. In alpha-chloralose- and urethane-anesthetized rats, microinjection of glutamate and N-methyl-D-aspartate (NMDA; 50, 100, and 200 pmol) into the PVN produced dose-dependent increases in renal sympathetic nerve activity, blood pressure, and heart rate. These responses were blocked by the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (AP-5). Microinjection of bicuculline, a GABA(A) receptor antagonist, into the PVN (50, 100, and 200 pmol) also produced significant, dose-dependent increases in renal sympathetic nerve activity, blood pressure, and heart rate; AP-5 also blocked these responses. Using microdialysis and HPLC/electrochemical detection techniques, we observed that bicuculline infusion into the PVN increased glutamate release. Using an in vitro hypothalamic slice preparation, we found that bicuculline increased the frequency of glutamate-mediated excitatory postsynaptic currents in PVN-rostral ventrolateral medullary projecting neurons, supporting a GABA(A)-mediated tonic inhibition of this excitatory input into these neurons. Together, these data indicate that 1) glutamate, via NMDA receptors, excites the presympathetic neurons within the PVN and increases sympathetic outflow and 2) this glutamate excitatory input is tonically inhibited by a GABA(A)-mediated mechanism.     

A Comparative Study of Excitatory and Inhibitory Amino Acids in Three Different Brainstem Nuclei

This study was designed to shed more light onto the three different brainstem regions which are implicated in the pain pathway for the level of various excitatory and inhibitory neurotransmitters before and following neuronal stimulation. The in vivo microdialysis technique was used in awake, freely moving adult Sprague-Dawley rats. The neurotransmitters studied included aspartate, glutamate, GABA, glycine, and taurine. The three brainstem regions examined included the mid-brain periaqueductal gray (PAG), the medullary nucleus raphe magnus (NRM), and the spinal trigeminal nucleus (STN). Neuronal stimulation was achieved following the administration of the sodium channel activator veratridine. The highest baseline levels of glutamate (P < 0.0001), aspartate (P < 0.0001), GABA (P < 0.01), taurine (P < 0.0001), and glycine (P < 0.001) were seen in the NRM. On the other hand, the lowest baseline levels of glutamate, GABA, glycine, and taurine were found in the PAG, while that of aspartate was found in the STN. Following the administration of veratridine, the highest release of the above neurotransmitters except for the aspartate and glycine was found in the PAG where the level of glutamate increased by 1,310 ± 293% (P < 0.001), taurine by 1,008 ± 143% (P < 0.01), and GABA by 10,358 ± 1,920% (P < 0.0001) when comparison was performed among the three brainstem regions and in relation to the baseline levels. The highest release of aspartate was seen in the STN (2,357 ± 1,060%, P < 0.001), while no significant difference was associated with glycine. On the other hand, the lowest release of GABA and taurine was found in the STN (696 ± 91 and 305 ± 25%, respectively), and glutamate and aspartate in the NRM (558 ± 200 and 874 ± 315%, respectively). Our results indicate, and for the first time, that although some differences are seen in the baseline levels of the above neurotransmitters in the three regions studied, there are quite striking variations in the level of release of these neurotransmitters following neuronal stimulation in these regions. In our opinion this is the first study to describe the pain activation/modulation related changes of the excitatory and inhibitory amino acids profile of the three different brainstem areas.     

Primitive nervous systems: Action of aminergic drugs and blocking agents on activity in the ventral nerve cord of the flatworm Notoplana acticola

Electrically evoked activity in the submuscular ventral longitudinal nerve cords of Notoplana acticola is depressed by GABA and glycine in the presence of high magnesium concentrations. This inhibition occurs with 0.001–0.01 millimolar concentrations of these putative aminergic neurotransmitters and is reversible when washed out. The action of GABA and glycine was reversed nonspecifically by picrotoxin, bucuculline, and strychnine. PTZ (Pentylenetetrazole) was shown to mimic the effects that these blocking agents had on evoked activity when they were tested alone. The release of inhibition by these blocking agents is similar to that of decerebration. Three possible mechanisms responsible for synaptic activity in high Mg²⁺ concentrations are discussed and the possibility that the effector site of interaction may be the chloride ionophore is explored.     

Primitive nervous systems: action of aminergic drugs and blocking agents on activity in the ventral nerve cord of the flatworm Notoplana acticola.

Electrically evoked activity in the submuscular ventral longitudinal nerve cords of Notoplana acticola is depressed by GABA and glycine in the presence of high magnesium concentrations. This inhibition occurs with 0.001--0.01 millimolar concentrations of these putative aminergic neurotransmitters and is reversible when washed out. The action of GABA and glycine was reversed nonspecifically by picrotoxin, bicuculline, and strychnine. PTZ (Pentylenetetrazole) was shown to mimic the effects that these blocking agents had on evoked activity when they were tested alone. The release of inhibition by these blocking agents is similar to that of decerebration. Three possible mechanisms responsible for synaptic activity in high Mg2+ concentrations are discussed and the possibility that the effector site of interaction may be the chloride ionophore is explored.     

Spinal GABA(A) receptors do not mediate the sympathetic baroreceptor reflex in the rat

Activation of baroreceptors causes efferent sympathetic nerve activity (SNA) to fall. Two mechanisms could account for this sympathoinhibition: disfacilitation of sympathetic preganglionic neurons (SPN) and/or direct inhibition of SPN. The roles that spinal GABA and glycine receptors play in the baroreceptor reflex were examined in anesthetized, paralyzed, and artificially ventilated rats. Spinal GABA(A) receptors were blocked by an intrathecal injection of bicuculline methiodide, whereas glycine receptors were blocked with strychnine. Baroreceptors were activated by stimulation of the aortic depressor nerve (ADN), and a somatosympathetic reflex was used as control. After an intrathecal injection of vehicle, there was no effect on any measured variable or evoked reflex. In contrast, bicuculline caused a dose-dependent increase in arterial pressure, SNA, phrenic nerve discharge, and it significantly facilitated the somatosympathetic reflex. However, bicuculline did not attenuate either the depressor response or sympathoinhibition evoked after ADN stimulation. Similarly, strychnine did not affect the baroreceptor-induced depressor response. Thus GABA(A) and glycine receptors in the spinal cord have no significant role in baroreceptor-mediated sympathoinhibition.     

GABA参与兔杏仁体抑制内膝体神经元电活动

本文采用多管微电极胞外记录技术观察了短纯音引起兔内膝神经元的声反应及刺激杏仁体对声反应的影响,并在此基础上观察电泳ＧＡＢＡ及其拮抗剂Ｂｉｃｕｃｕｌｌｉｎｅ的效应。实验结果表明：ＧＡＢＡ可以抑制ＭＧＢ神经元的声反应及自发放电活动,而ＧＡＢＡＡ拮抗剂Ｂｉｃｕｃｕｌｌｉｎｅ的作用则相反;电泳ＧＡＢＡ对ＭＧＢ神经元产生同刺激杏仁体一样的抑制产应,并且这种影响可被Ｂｉｃｕｃｕｌｌｉｎｅ翻转;嗅鼻沟后缘听区农     

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

Summary In the barn owl (Tyto alba), the posterior nucleus of the ventral lateral lemniscus (VLVp) is the first site of binaural convergence in the pathway that processes interaural level difference (ILD), an important sound-localization cue. The neurons of VLVp are sensitive to ILD because of an excitatory input from the contralateral ear and an inhibitory input from the ipsilateral ear. A previously described projection from the contralateral cochlear nucleus, can account for the excitation. The present study addresses the source of the inhibitory input.We demonstrate with standard axonal transport methods that the left and right VLVps are interconnected via fibers of the commissure of Probst. We further show that the anesthetization of one VLVp renders ineffective the inhibition that is normally evoked by stimulation of the ipsilateral ear. Thus, one cochlear nucleus (driven by the ipsilateral ear) appears to provide inhibition to the ipsilateral VLVp by exciting commissurally-projecting inhibitory neurons in the contralateral VLVp.Abbreviations ABL average binaural level - CP commissure of Probst - DNLL dorsal nucleus of the lateral lemniscus - IC inferior colliculus - ILD interaural level difference - IPc nucleus isthmi, pars parvocellularis - ITD interaural time difference - LSO lateral superior olive - MNTB medial nucleus of the trapezoid body - NA nucleus angularis - SL nucleus semilunaris - VLVa nucleus ventralis lemnisci lateralis, pars anterior - VLVp nucleus ventralis lemnisci lateralis, pars posterior     

GABAergic inhibition shapes frequency tuning and modifies response properties in the auditory midbrain of the leopard frog

The functional role of GABAergic inhibition in shaping the frequency tuning of 96 neurons in the torus semicircularis of the leopard frog, Rana pipiens, was studied using microiontophoresis of the GABA_A receptor antagonist, bicuculline methiodide. Bicuculline application abolished, or reduced in size, the inhibitory tuning curves of 72 neurons. In each case, there was a concommitant broadening of the excitatory tuning curve such that frequency-intensity combinations that were inhibitory under control conditions, became excitatory during disinhibition with bicuculline methiodide. These effects were observed irrespective of the excitatory tuning curve configuration prior to bicuculline methiodide application. Results indicate an important role for GABA-mediated inhibition in shaping the frequency selectivity of neurons in the torus semicircularis of the leopard frog. Bicuculline application also affected several other response properties of neurons in the leopard frog torus. Disinhibition with bicuculline methiodide increased both the spontaneous firing rate (18 cells) and stimulus-evoked discharge rate (81 cells) of torus neurons, decreased the minimum excitatory threshold for 18 cells, and altered the temporal discharge pattern of 47 neurons. Additional roles for GABAergic inhibition in monaural signal analysis are discussed. Accepted: 25 August 1999     

Frequency tuning and response latencies at three levels in the brainstem of the echolocating bat,Eptesicus fuscus

To determine the level at which certain response characteristics originate, we compared monaural auditory responses of neurons in ventral cochlear nucleus, nuclei of lateral lemniscus and inferior colliculus. Characteristics examined were sharpness of frequency tuning, latency variability for individual neurons and range of latencies across neurons.Exceptionally broad tuning curves were found in the nuclei of the lateral lemniscus, while exceptionally narrow tuning curves were found in the inferior colliculus. Neither specialized tuning characteristic was found in the ventral cochlear nuclei.All neurons in the columnar division of the ventral nucleus of the lateral lemniscus maintained low variability of latency over a broad range of stimulus conditions. Some neurons in the cochlear nucleus (12%) and some in the inferior colliculus (15%) had low variability in latency but only at best frequency.Range of latencies across neurons was small in the ventral cochlear nucleus (1.3–5.7 ms), intermediate in the nuclei of the lateral lemniscus (1.7–19.8 ms) and greatest in the inferior colliculus (2.9–42.0 ms).We conclude that, in the nuclei of the lateral lemniscus and in the inferior colliculus, unique tuning and timing properties are built up from ascending inputs.Abbreviations AVCN anteroventral cochlear nucleus - BF best frequency - CV coefficient of variation - DCN dorsal cochlear nucleus - FM frequency modulation - IC inferior colliculus - NLL nuclei of lateral lemniscus - PSTH post stimulus time histogram - PVCN posteroventral cochlear nucleus - SD standard deviation - SPL sound pressure level - VCN ventral cochlear nuclei - VNLLc ventral nucleus of the lateral lemniscus, columnar division     

刺激面神经核对前包钦格复合体呼吸神经元放电活动的影响及其递质机制

实验选用健康成年SD大鼠,观察电刺激面神经核对前包钦格复合体(pre-—Boetzinger complex,PBC)呼吸神经元(RNs)放电活动的影响,并观察微电泳6-氰基-7-硝基喹喔啉-2,3-二酮(CNQX)、荷包牡丹碱(BIC)、士的宁(Stry)和阿托品(Atr)对电刺激面神经核引起的PBCRNs放电变化的拮抗效应,以进一步探讨面神经核是否参与呼吸调节及其可能的神经机制。在12只面运动神经元逆行溃变大鼠同侧PBC内共记录到各类RNs116个,电刺激溃变侧面神经核时,前吸气(Pre-I)神经元(24／26个)和吸气(I)神经元(30／35个)主要表现为兴奋,呼气(E)神经元(20／22个)和吸气-呼气(I-E)跨时相神经元(28／33个)表现为抑制。CNQx可完全或部分拮抗电刺激面神经核对Pre-I(18／24)和I(23／27)神经元的兴奋效应;Stry可拮抗电刺激面神经核对Pre-I(12／18)和I(14／23)神经元的瞬时抑制效应以及对I-E(20／28)和E(9／16)神经元的抑制效应;BIC可拮抗电刺激面神经核对I—E(22／25)和E(9／9)神经元的抑制效应;微电泳Atr对各类RNs的放电变化无明显作用。这些结果表明,面神经核非运动神经元可能通过向PBC的纤维投射,以Glu、GABA和Gly为神经递质或调质,调节PBC RNs的活动,从而参与对呼吸运动的调节。     

Zinc modulation of glycine receptors in acutely isolated rat CA3 neurons

Glycine and GABA are the primary inhibitory neurotransmitters in the spinal cord and brain stem, with glycine exerting its physiological roles by activating strychnine-sensitive ionotropic receptors. Glycine receptors are also expressed in the brain, including the cortex and hippocampus, but their physiological roles and pharmacological properties are largely unknown. Here, we report the pharmacological properties of functional glycine receptors in acutely isolated rat CA3 neurons using conventional whole-cell patch clamp techniques. Both glycine and taurine, which are endogenous agonists of glycine receptors, elicited Cl(-) currents in a concentration-dependent manner. The glycine-induced current (I(Gly)) was inhibited by strychnine, picrotoxin or cyclothiazide in a concentration-dependent manner. At lower concentrations (0.01-1 microM), ICS-205,930 potentiated I(Gly), but at higher concentrations (>10 microM) it inhibited I(Gly). These pharmacological properties strongly suggest that CA3 neurons express functional strychnine-sensitive glycine receptors containing alpha2 subunits. Furthermore, at lower concentrations (1-30 microM), Zn(2+) potentiated I(Gly), but at higher concentrations (>100 microM) it inhibited I(Gly). Considering that Zn(2+) is synaptically co-released with glutamate from mossy fiber terminals that make excitatory synapses onto CA3 neurons, these results suggest that endogenous Zn(2+) modulation of these glycine receptors may have an important role in the excitability of CA3 neurons.     

Gamma-aminobutyric acid and GABAA receptors are involved in directional selectivity of pretectal neurons in pigeons

The present study describes the effects of gamma-aminobutyric acid (GABA) and its antagonists, bicuculline and 2-hydroxysaclofen, on visual responses of neurons in the pigeon nucleus lentiformis mesencephali (nLM). The results indicate that GABA significantly reduces both spontaneous activity and visual responsiveness, and GABA_A antagonist bicuculline but not GABA_B antagonist 2-hydroxysaclofen enhances visual responses of nLM cells examined. Furthermore, inhibition produced by motion in the null-direction of pretectal neurons is diminished by bicuculline but not by 2-hydroxysaclofen. It is therefore concluded that the null-direction inhibition of directional cells in the pigeon nLM is predominantly mediated by GABA and GABA_A receptors. This inhibition may at least in part underlie directional asymmetry of optokinetic responses.