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.     

锐化蝙蝠听皮层神经元频率调谐的柱特征

用双声刺激和多管电极方法在 6只大棕蝠 (bigbrownbat,Eptesicusfuscus)的 98个神经元上研究了锐化 (sharpening)蝙蝠听皮层 (primaryauditorycortex ,AC)神经元频率调谐的柱特征。结果发现 ,电极直插在 1个电极通道内连续记录到多个神经元时 ,它们锐化频率调谐的抑制性调谐曲线或抑制区基本相似。电极与AC表面呈 45°斜向推入使其跨越多个功能柱时 ,可观察到锐化频率调谐的抑制区构成也随电极进入不同的功能柱而发生相应的改变。两种不同的电极插入方式均证明锐化AC神经元频率调谐的神经抑制呈柱状组构。这些神经元组合起来排列在同一听觉功能柱内 ,构成AC频率分析的基本功能组构单位“微频率处理器”。实验中还观察到多峰频率调谐曲线神经元 ,它们在声通讯和声定位中不同波谱区域的时间匹配中起作用。此外 ,也有理由认为多峰调谐神经元亦被用于作为复杂波谱信息的“高级调谐预处理器” ,从而极大地提高了神经元对频率分析的能力。为研究锐化频率调谐的神经抑制机制 ,用多管电极电泳γ -氨基丁酸 (γ aminobutyricacid ,GA BA)能a受体拮抗剂荷包牡丹碱 (bicuculline ,Bic)至所记录的神经元 ,发现能大部分或几乎全部取消抑制区 ,从而表明在正常情况下GABA能抑制参与构成锐化AC神经元频率调谐的抑制区 ,     

蛙下丘频率调谐特性方向选择性的建模和仿真

基于Ｆｅｎｇ等人的神经电生理实验结果,建立了关于豹蛙（Ｒａｎａ ｐｉｐｉｅｎ）半规隆凸（ｔｏｒｕｓ ｓｅｍｉｃｉｒｃｕｌａｒｉｓ）核团神经元频率调谐特性方向选择性反应的模型,并在此基础上讨论了模型各个参数对模型方向性反应输出的影响。结果提示：１）听觉系统两侧的相互抑制作用－双耳抑制主要决定频率调谐特性的尖锐性随方向变化的特性;２）前级神经元对不同方位外界声源刺激具有不同强度平均脉冲发放的特征则主要     

The functional role of GABA and glycine in monaural and binaural processing in the inferior colliculus of horseshoe bats

Summary The functional role of GABA and glycine in monaural and binaural signal analysis was studied in single unit recordings from the central nucleus of the inferior colliculus (IC) of horseshoe bats (Rhinolophus rouxi) employing microiontophoresis of the putative neurotransmitters and their antagonists bicuculline and strychnine.Most neurons were inhibited by GABA (98%; N=107) and glycine (92%; N=118). Both neurotransmitters appear involved in several functional contexts, but to different degrees.Bicuculline-induced increases of discharge activity (99% of cells; N=191) were accompanied by changes of temporal response patterns in 35% of neurons distributed throughout the IC. Strychnine enhanced activity in only 53% of neurons (N=147); cells exhibiting response pattern changes were rare (9%) and confined to greater recording depths. In individual cells, the effects of both antagonists could markedly differ, suggesting a differential supply by GABAergic and glycinergic networks.Bicuculline changed the shape of the excitatory tuning curve by antagonizing lateral inhibition at neighboring frequencies and/or inhibition at high stimulation levels. Such effects were rarely observed with strychnine.Binaural response properties of single units were influenced either by antagonization of inhibition mediated by ipsilateral stimulation (bicuculline) or by changing the strength of the main excitatory input (bicuculline and strychnine).Abbreviations BF best frequency - Bic bicuculline - C control - CF constant frequency - CN cochlear nucleus - DNLL dorsal nucleus of the lateral lemniscus - FM frequency modulation - GABA gamma amino butyric acid - IC inferior colliculus - LSO lateral superior olive - Str strychnine     

Bicuculline application affects discharge pattern and pulse-duration tuning characteristics of bat inferior collicular neurons

This study examines the contribution of GABAergic inhibition to the discharge pattern and pulse duration tuning characteristics of 101 bat inferior collicular neurons by means of bicuculline application to their recording sites. When stimulated with single pulses, 56 (55%) neurons discharged 1 or 2 impulses (phasic responders), 42 (42%) discharged 3–10 impulses (phasic bursters) and 3 (3%) discharged impulses throughout the stimulus duration (tonic responders). Bicuculline application increased the number of impulses and changed the discharge patterns of 66 neurons. Using 50% difference between maximal and minimal responses as a criterion, the duration tuning characteristics of these neurons can be described as band-pass (20, 20%), long-pass (17, 17%), short-pass (33, 32%), and all-pass (31, 31%). Each band-pass neuron discharged maximally to a specific duration (the best duration) which was at least 50% larger than the neuron's responses to a long-duration pulse and a short-duration pulse. In contrast, each long- or short-pass neuron discharged maximally to a range of long or short duration pulses. Bicuculline application changed the duration tuning characteristics of 65 neurons. Possible mechanisms underlying duration tuning characteristics and the behavioral relevance to bat echolocation are discussed. Accepted: 4 November 1998     

GABAergic inhibition shapes temporal and spatial response properties of pyramidal cells in the electrosensory lateral line lobe of gymnotiform fish

1. The amplitude-coding pyramidal neurons of the first-order nucleus in weakly electric gymnotiform fish (Eigenmannia), the electrosensory lateral line lobe (ELL), exhibit 2 major physiological transformations of primary afferent input. Pyramidal cells rapidly adapt to a step change in amplitude, and they have a center/surround receptive-field organization. This study examined the physiological role of GABAergic inhibition on pyramidal cells. GABAergic synapses onto the somata of pyramidal cells primarily originate from granule-cell interneurons along with descending input. 2. Pyramidal cells fall into two physiologically distinct categories: E units, which are excited by a rise in stimulus amplitude, and I units, which are inhibited by a rise in stimulus amplitude. Microiontophoretic application of bicuculline methiodide onto both types of pyramidal cells increased the time constant of adaptation, defined as the time required for the neuron's response to decay to 37% of its maximum value, by 70-90%. The peak firing rate of E units to a step increase in stimulus amplitude increased by 49%, while the firing rate of I units did not change significantly. 3. Bicuculline application demonstrated that GABAergic inhibition may contribute to the strict segregation of E and I response properties. In the presence of bicuculline, many E units (normally excited only by stimulus amplitude increases) became excited by both increases and decreases; many I units (normally excited only by amplitude decreases) also became excited to increases. 4. The size of the excitatory receptive-field of E units was not affected by bicuculline, although response magnitude increased. The inhibitory surround increased in spatial extent by 175% with bicuculline administration. Neither the size of the I unit receptive-field center nor the response magnitude changed in the presence of bicuculline. The antagonistic surround of I units, however, increased by 49%. 5. The anatomy of the ELL is well understood (see Carr and Maler 1986). The physiological results obtained in this study, along with the results of Bastian (1986a, b), further our understanding of the functional role of the ELL circuitry. Our results suggest that spatial and temporal response properties of pyramidal cells are regulated by different but interacting inhibitory interneurons, some of which use GABA as a neurotransmitter. The activity of these interneurons is in turn controlled by descending feedback systems.     

Lateral sharpening of cortical frequency tuning by approximately balanced inhibition

Cortical inhibition plays an important role in shaping neuronal processing. The underlying synaptic mechanisms remain controversial. Here, in vivo whole-cell recordings from neurons in the rat primary auditory cortex revealed that the frequency tuning curve of inhibitory input was broader than that of excitatory input. This results in relatively stronger inhibition in frequency domains flanking the preferred frequencies of the cell and a significant sharpening of the frequency tuning of membrane responses. The less selective inhibition can be attributed to a broader bandwidth and lower threshold of spike tonal receptive field of fast-spike inhibitory neurons than nearby excitatory neurons, although both types of neurons receive similar ranges of excitatory input and are organized into the same tonotopic map. Thus, the balance between excitation and inhibition is only approximate, and intracortical inhibition with high sensitivity and low selectivity can laterally sharpen the frequency tuning of neurons, ensuring their highly selective representation.     

Seasonal changes in frequency tuning and temporal processing in single neurons in the frog auditory midbrain

Frogs rely on acoustic signaling to detect, discriminate, and localize mates. In the temperate zone, reproduction occurs in the spring, when frogs emerge from hibernation and engage in acoustically guided behaviors. In response to the species mating call, males typically show evoked vocal responses or other territorial behaviors, and females show phonotactic responses. Because of their strong seasonal behavior, it is possible that the frog auditory system also displays seasonal variation, as evidenced in their vocal control system. This hypothesis was tested in male Northern leopard frogs by evaluating the response characteristics of single neurons in the torus semicircularis (TS; a homolog of the inferior colliculus) to a synthetic mating call at different times of the year. We found that TS neurons displayed a seasonal change in frequency tuning and temporal properties. Frequency tuning shifted from a predominance of TS units sensitive to intermediate frequencies (700-1200 Hz) in the winter, to low frequencies (100-600 Hz) in the summer. In winter and early spring, most TS neurons showed poor, or weak, time locking to the envelope of the amplitude-modulated synthetic call, whereas in late spring and early summer the majority of TS neurons showed robust time-locked responses. These seasonal differences indicate that neural coding by auditory midbrain neurons in the Northern leopard frog is subject to seasonal fluctuation.     

Role of intracortical inhibition in orientation tuning dynamics in the cat striate cortex neurons

A suggestion about the leading role of GABA-induced intracortical inhibition in the dynamics of orientation tuning (OT) of the cat striate cortical neurons was tested in acute experiments before and during the local blockade of their inhibition by iontophoretic application of bicucculine. In the course of the investigation of these dynamics, with the use of a temporal scanning method, two types of neurons differing in the inhibition blockade-induced OT changes were found. In the neurons of the first type (57%), bicuculline induced the OT dynamics or enhanced it, if it pre-existed before the bicuculline application. In the neurons of the second type (43%), bicuculline strongly reduced or eliminated the dynamic shift of a preferred orientation. These results mean that under normal conditions the inhibition stabilizes and sharpens OT in some cells, while in other cells, in contrast, it causes the OT dynamics. The following mechanisms may underlie the observed effects: an elimination of the inhibition originating from lateral non-isoorientational excitatory inputs of a receptive field; an inhibition of these inputs via the adjacent interneurons activated by a powerful discharge of the examined neuron; a long-term afterhyperpolarization of the neuron, and the dynamics of the excitatory and inhibitory zones of the receptive field.Neirofiziologiya/Neurophysiology, Vol. 27, No. 2, pp. 100–109, March–April, 1995.     

γ-氨基丁酸能抑制对大棕蝠听皮层神经元声反应特性的影响

为了探讨γ－氨基丁酸（γ-aminobutyric acid,GABA)能抑制对大棕蝠(Eptesicus fuscus)听皮层(auditory cortex,AC)神经元声反应特性的影响,采用多管微电极电泳方法,观察了8只大棕蝠AC神经元去ABA能抑制前后声刺激诱发的反应。结果显示,微电泳GABAa受体拮抗剂荷包牡丹碱(bicuculline,Bic)去ABA能抑制可改变声刺激诱发的反应模式;极大地增加神经元冲动发放率,缩短反应的潜伏期和降低反应的最小阈值;不同程度地改变强度－发放率和强度－潜伏期函数。结果提示：1、GABA能抑制对AC神经元声信号处理起重要作用;2、GABA能抑制可改变AC神经元兴奋性支配或输入的效应,并因此定型AC神经元的声反应性质,即发放模式、阈值、强度－发放率和强度－潜伏期函数;3、GABA能抑制为AC神经元的声诱发活动提供一种调制性抑制。     

Contribution of GABAA receptor-mediated inhibition to the determination of the velocity tuning of low pass-tuned neurons of the Superior Colliculus

The participation of intrinsic inhibitory networks in providing the velocity selectivity of neurons of the superior colliculus (SC) of the Syrian hamster was tested using iontophoretic application of bicuculline methiodide, a GABA_A receptor competitive antagonist. The impulse activity of 22 low pass-tuned (LP) cells was recorded extracellularly. Following application of bicuculline, 10 cells exhibited an increase in the velocity selectivity, while the other 12 units showed decreases in their tuning. We assume that SC intrinsic inhibitory networks contributing to the velocity tuning of neurons of this structure are driven in a dissimilar way by afferent volleys arriving from the retina through “fast” Y and “slow” W channels. Neirofiziologiya/Neurophysiology, Vol. 39, Nos. 4/5, pp. 385–387, July–October, 2007.     

Morphology of neurons in the torus semicircularis of the northern leopard frog,Rana pipiens pipiens

The neuronal morphology of the torus semicircularis of the northern leopard frog, Rana pipiens pipiens, was examined in Golgi-impregnated material. Neurons in each of the five subdivisions of the torus semicircularis (Potter, '65a) have distinct morphologies which are characteristic of the subdivision. Laminar nucleus neurons are mostly multipolar with spherical or ovoidal somata and smooth dendrites oriented primarily parallel and perpendicular to the cell laminae. Principal nucleus neurons have variable soma shapes with short dendrites ( < 100 μm) radiating in all directions. In the magnocellular nucleus, there are three major cell types: neurons characterized by small, spherical-shaped somata, with short, thin, radiating dendrites and many varicosities; bi- or tripolar neurons with ovoidal somata, and long (100–200 μm) and smooth dendrites orienting primarily dorsoventrally and mediolaterally; and multipolar neurons with triangular-shaped somata and very long (200–350 μm) dendrites, which are either smooth or highly spiny. Neurons in the commissural nucleus are mostly multipolar cells with ovoidal somata and beaded dendrites projecting mostly dorsally and ventrally. The subependymal midline nucleus contains mostly uni- or bipolar neurons with small ovoidal somata and straight, spiny dendrites. In addition to revealing the morphological features of neurons in the torus, the counterstained material shows further cytoarchitectural organization of the principal nucleus, i.e., the presence of a circular lamellar organization. The functional significance of these anatomical features is discussed.     

小鼠初级听皮质神经元的强度调谐特性与机制分析

强度是声音的基本参数之一,听神经元的强度调谐在听觉信息处理方面具有重要意义．以往研究发现γ-氨基丁酸(γ-aminobutyric acid, GABA)能抑制性输入在强度调谐的形成过程中起重要作用,但对抑制性输入与局部神经回路之间的关系并不清楚．本实验通过在体细胞外电生理记录和神经药理学方法,分析了小鼠初级听皮质神经元的强度调谐特性,结果显示：单调型神经元在声刺激强度自中等强度增高时潜伏期缩短(P < 0.05)且发放持续时间延长(P < 0.05),非单调型神经元在声刺激强度自最佳强度增高时潜伏期不变且发放持续时间缩短(P < 0.01)．注射GABA能阻断剂荷包牡丹碱(bicuculline, Bic)后,39.3%的神经元强度调谐类型不变,42.9%的神经元非单调性减弱,17.9%的神经元非单调性增强．表明GABA能抑制并非是形成非单调性的唯一因素,兴奋性输入本身的非单调性和高阈值非GABA能抑制的激活也可能在其中发挥作用．推测由兴奋性和抑制性输入所构成的局部神经功能回路及其整合决定了听皮质神经元的强度调谐特性．     

GABAergic disinhibition changes the recovery cycle of bat inferior collicular neurons

This study examines the contribution of GABAergic inhibition to the discharge pattern and recovery properties of 110 bat inferior collicular neurons by means of bicuculline application to their recording sites. When stimulated with single pulses, 74 (67%) neurons discharged one or two impulses (phasic responders), 19 (17%) discharged three to ten impulses (phasic bursters) and 17 (16%) discharged impulses throughout the entire stimulus duration (tonic responders). Bicuculline application changed phasic responders into phasic bursters or tonic responders, increased the number of impulses by 10–2000% and shortened the response latency of most neurons. When stimulated with pairs of sound pulses, the recovery cycles of these neurons can be described as: (1) long inhibition (n = 49, 45%); (2) short inhibition (n = 41, 37%); and (3) fast recovery (n = 20, 18%) based upon the 50% recovery time that was either longer than 20 ms, between 10 and 20 ms or shorter than 10 ms. Bicuculline application shortened the 50% recovery time of most neurons by 11–2350% allowing them to respond to pairs of sound pulses at very short interpulse intervals. These data demonstrate that GABAergic inhibition contributes significantly to auditory temporal processing. Accepted: 18 April 1997     

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     

Bicuculline对小鼠中脑下丘听神经元

采用微电泳技术考察了GABAA受体拮抗剂荷包牡丹碱（bicuculline）,对小鼠中脑下丘听神经元强度-放电率曲线、频率调谐曲线和听空间反应域的影响。结果表明,微电泳bicuculline使听神经元的放电率显著提高,多数神经元的强度-放电率曲线变为单调型;听神经元频率调谐曲线加宽,并且对曲线上部的作用更加明显;听神经元的听空间反应域增大,方向敏感性降低。实验结果提示了GABA能抑制在下丘听信息处理中的重要作用。     

GABA拮抗剂荷包牡丹碱对猫外膝体神经元方位调谐特性的影响

在十二只成年猫上用多管玻璃微电极记录了外膝体神经元对不同空间频率和不同方位的移动正弦光栅刺激的反应,共详细测定并对比研究了３８个方位敏感性细胞在微电泳荷包牡丹碱前后的方位调谐特性。在最优空间频率附近的较低空间频率下,微电泳荷包牡丹碱后,外膝体细胞的方位敏感性强度（Ｂｉａｓ）降低,而在截止频率附近的较高空间频率下,微电泳前后外膝细胞的方位敏感性强度（Ｂｉａｓ）从总体上看没有显著变化。结果表明,以空间频率为截止频率附近的移动正弦光栅作为刺激,外膝体细胞的方位敏感性可能主要是由视网膜神经节细胞的兴奋输入所形成,而非外膝体内抑制机制所致。     

GABA-mediated modulation of the discharge pattern and rate-level function of two simultaneously recorded neurons in the inferior colliculus of the big brown bat, Eptesicus fuscus

Neurons in the central nucleus of the inferior colliculus (IC) receive excitatory and inhibitory inputs from both lower and higher auditory nuclei. Interaction of these two opposing inputs shapes response properties of IC neurons. In this study, we examine the interaction of excitation and inhibition on the responses of two simultaneously recorded IC neurons using a probe and a masker under forward masking paradigm. We specifically study whether a sound that serves as a probe to elicit responses of one neuron might serve as a masker to suppress or facilitate the responses of the other neuron. For each pair of IC neurons, we deliver the probe at the best frequency (BF) of one neuron and the masker at the BF of the other neuron and vice versa. Among 33 pairs of IC neurons recorded, this forward masking produces response suppression in 29 pairs of IC neurons and response facilitation in 4 pairs of IC neurons. The degree of suppression decreases with recording depth, sound level and BF difference between each pair of IC neurons. During bicuculline application, the degree of response suppression decreases in the bicuculline-applied neuron but increases in the paired neuron. Our data indicate that the forward masking of responses of IC neurons observed in this study is mostly mediated through GABAergic inhibition which also shapes the discharge pattern of these neurons. These data suggest that interaction among individual IC neurons improves auditory sensitivity during auditory signal processing.     

Distribution of GABA-immunoreactive neurons in the brain of adult and developing salamanders (Pleurodeles waltli,Triturus alpestris)

The distribution of GABAergic neurons in brains of the family Salamandridae (Pleurodeles waltli, Triturus alpestris) has been investigated immunohistochemically with an antibody against gamma-aminobutyric acid (GABA). In adult animals, immunoreactive neurons, fibers, and terminals are abundantly labeled. In the telencephalon, pallial areas contain fewer GABAergic neurons and fibers than basal forebrain areas. The amygdalar complex and the habenulae have a complex pattern of GABA-immunoreactivity that is especially pronounced within the neuropil. The pretectal and basal optic systems are provided with GABAergic neurons, corroborating electrophysiological results. The dorsal thalamus and parts of the torus semicircularis are almost completely devoid of GABA-immunoreactive neurons. In the torus, magnocellular neurons known to project to the contralateral counterpart are distinctly GABA-immunoreactive. During ontogeny, GABAergic neurons arise early when the first reflexive movements occur after mechanical stimulation. At stage 28, cells are labeled initially near the nucleus of the medial longitudinal fasciculus, which is the first supraspinal tract to appear in ontogeny. At stage 30 (still before hatching), GABAergic neurons are found in the pretectum, immunoreactive neurons arising in the dorsal tegmentum slightly later. Both systems are known to mediate basic reflexes in gaze stabilization. The commissura posterior is GABAergic at early stages suggesting an important functional role in homonymous inhibition between both sides. Thus in salamanders, the neurotransmitter GABA displays a complex distribution, similar to that in other vertrebrates. This pattern emerges early in ontogeny.     

Interference with the GABAergic system in the dorsolateral telencephalon and modulation of the electric organ discharge frequency in the weakly electric fish Gymnotus carapo

The functional role of the dorsal portions of dorsolateral telencephalon in modulating the stable electric organ discharge was determined by microinjection of an agonist or antagonist GABAergic drug in the awake weak electric fish, Gymnotus carapo. The dorsolateral telencephalon, which is interconnected with the preglomerular complex and the dorsocentral telencephalic area was microinjected through a guide cannula previously implanted, with different doses of bicuculline, muscimol and saline. Microinjection of bicuculline into the dorsolateral telencephalon induced a complex response consisting of increase, decrease and abrupt interruptions in the frequency of electric organ discharges and an increase in motor activity. Motor activity and modulations in the electric organ discharge are dose dependent. The somatic, but not the electric, effect is abolished under anesthesia by urethane, suggesting that the two responses are parallel but unrelated in terms of occurrence. These data, together with former neuroanatomical findings by this laboratory, suggest two parallel pathways by which the blockage of GABAA receptors in the dorsolateral telencephalon causes modulations in the firing of the medullary pacemaker nucleus. A possible route for the motor effect through reticular projection from the torus semicircularis dorsalis is discussed.