Iontophoretic Application Of Bicuculline Research Articles

GABA Is Involved in Spatial Unmasking in the Frog Auditory Midbrain

Real-world listening situations comprise multiple auditory objects. Sounds originating from different objects are summated at the eardrum. The auditory system therefore must segregate the streams of sounds associated with the different objects. One listening strategy in complex environments is to attend to signals originating from one spatial location. In doing so, signal detection is compromised when a masker is present at close proximity, and detection is improved if the masker is spatially separated from the signal. A recent study has shown that, in frogs, spatial unmasking is more robust at the midbrain than at the periphery, indicating the importance of central mechanisms for this process. In this study, we investigated spatial unmasking patterns of single neurons in the frog inferior colliculus (IC) before and during iontophoretic application of bicuculline, a GABA(A) receptor antagonist. We found that drug application markedly decreased the strength of spatial unmasking such that even large angular separation of signal and masker sources produced only a weak masking release. Under the drug, the strength of spatial unmasking of midbrain neurons approximated that of auditory nerve fibers. These data show that GABAergic interactions in the auditory midbrain play an important role in spatial unmasking. Analysis of the effect of the drug on the direction sensitivity of the units shows that for the majority of IC units, bicuculline degrades binaural processing involved in directional coding, thereby compromising spatial unmasking. For other IC units, however, the decline in the strength of spatial unmasking is attributable to the effects of bicuculline on different central auditory processes.

The effect of bicuculline application on azimuth-dependent recovery cycle of inferior collicular neurons of the big brown bat, Eptesicus fuscus

The recovery cycle of auditory neurons is an important neuronal property, which determines a neuron’s ability to respond to pairs of sounds presented at short inter-sound intervals. This property is particularly important for bats, which rely upon analysis of returning echoes to extract the information about targets after emission of intense orientation sounds. Because target direction often changes throughout the course of hunting, the changing echo direction may affect the recovery cycle and thus temporal processing of auditory neurons. In this study, we examined the effect of sound azimuth on the recovery cycle of inferior collicular (IC) neurons in the big brown bat, Eptesicus fuscus, under free-field stimulation conditions. Our study showed that the recovery cycle of most IC neurons (42/49, 86%) was longer when determined with sounds delivered at 40° ipsilateral (i40°) than at 40° contralateral (c40°) to the recording site. To study the contribution of GABAergic inhibition to sound azimuth-dependent recovery cycle, we compared the recovery cycle of IC neurons determined at two sound azimuths before and during iontophoretic application of bicuculline, an antagonist for GABA A receptors. Bicuculline application produced a greater decrease of the recovery cycle of these neurons at i40° than at c40°. As a result, the azimuth-dependent recovery cycle of these neurons was abolished or greatly reduced. Possible mechanisms underlying these observations and biological relevance to bat echolocation are discussed.

Evidence of a functionally segregated pathway from dorsal cochlear nucleus to inferior colliculus.

Type O units in the central nucleus of the inferior colliculus (ICC) of decerebrate cats are excited by best frequency (BF) tones near threshold, but are inhibited by high-level tones at all frequencies. Dorsal cochlear nucleus (DCN) principal cells display similar response map features and project directly to the ICC, and are thus supposed to be the dominant source of excitatory input for type O units. To test this hypothesis, the responses of type O units were compared before and after two pharmacological manipulations. When DCN to ICC axons were blocked by pressure injections of lidocaine, most type O units (approximately 80%) were silenced or showed substantially reduced activity, but some units showed increased activity. All of the former units had low maximal rates to BF tones, whereas the latter units had high rates. When local circuit inhibitory mechanisms in the ICC were blocked by iontophoretic application of bicuculline or strychnine, type O unit responses also fell into two classes: low-rate units that showed increased spontaneous and driven activities and high-rate units that showed, in addition, altered response map features. Taken together, these results demonstrate that low-rate type O units are part of a functionally segregated pathway initiated by the DCN, whereas high-rate type O units are created at the level of the ICC.

Bicuculline attenuates the MLR-induced suppression of dorsal horn neurons receiving group III afferent input

In decerebrate cats, we found that iontophoretic application of bicuculline, a GABA A receptor antagonist, attenuated the mesencephalic locomotor region-induced suppression of dorsal horn neurons responding to group III afferent input from the hindlimb. Our findings raise the possibility that GABA release onto dorsal horn neurons in the spinal cord may play an important role in the attenuation of the exercise pressor reflex by central command during exercise.

Oscillation May Play a Role in Time Domain Central Auditory Processing

To study how sound intensity altered the temporal response pattern of a unit, we recorded from 92 single neurons in the inferior colliculus (IC) of the little brown bat and investigated their firing patterns in response to brief tone pulses (2 msec duration) at the characteristic frequency of the unit over a wide dynamic range (10-90 dB sound pressure level). We found two unusual response characteristics at high sound levels in approximately one-third of the IC neurons investigated. For 16 IC neurons (17%), an increase in sound level not only elicited a shorter response latency and an increase in spike count but also transformed the firing pattern of the unit from phasic to periodic; this pattern was more pronounced at higher sound levels. The firing periodicity was unit specific, ranging from 1.3 to 6.7 msec. Twenty-seven IC neurons (29%) exhibited a longer response latency at higher sound levels compared with lower sound levels [i.e., paradoxical latency shift (PLS)]. The majority of this population showed a one or more quantum increase in latency when sound level was elevated. The quantum shift was also unit specific, ranging from 1.2 to 8.2 msec. We further investigated the firing patterns of 14 IC neurons showing PLS before, during, and after iontophoretic application of bicuculline. For 12 of these neurons, drug application abolished the PLS and transformed the firing patterns of the unit at high sound levels from phasic into sustained periodic discharges. Our results suggest that neural oscillation in combination with ordinary inhibition may be responsible for the creation of PLSs shown previously to be important for temporal information processing.

Roles of neural oscillation in time domain processing in the bat inferior colliculus

Central auditory neurons in echolocating bats exhibit pulse-echo delay-tuned responses. Sullivan (1982) proposed that paradoxical latency shift (PLS), characterized by an increase in response latency to loud sounds, is important for this attribute. At present, the mechanism underlying PLS is unclear. The goal of the present study was to identify the mechanism underlying PLS. The responses of 92 neurons in the inferior colliculus of little brown bats to brief tone pulses at the unit’s CF over a wide range of sound levels were studied. Of these, 16 neurons displayed unit-specific periodic oscillatory discharges at high sound levels with a characteristic period of 1.3–6.7 ms. The 27 neurons exhibited unit-specific PLS, with quantal latency shift of 1.2–8.2 ms. In 14 neurons showing PLS, unit’s responses before, during and after iontophoretic application of bicuculline were investigated. Application of bicuculline abolished the PLS and transformed it into periodic discharges, suggesting that neural oscillation in combination with ordinary inhibition may be responsible for PLS. To further investigate whether intrinsic neural property was responsible for PLS, unit’s responses to sounds having different durations were investigated. The result indicates that both intrinsic and extrinsic mechanisms are likely involved in creation of PLS. [Work supported by NIH R01DC00663.]

Change in mechanical receptive field properties induced by GABA(A) receptor activation in the trigeminal spinal nucleus caudalis neurons in rats.

The purpose of the present study was to characterize the effect of a local GABAergic inhibitory mechanism on the mechanical receptive field properties of trigeminal spinal nucleus caudalis (SpVc) neurons by iontophoretic application of a gamma-aminobutyric acidA (GABA(A))-antagonist and -agonist. A total of 24 SpVc neurons that responded to orofacial mechanical stimulation were extracellularly recorded by means of multibarrel microelectrodes in urethane-anesthetized rats. The GABA(A) antagonist bicuculline (30 nA, 5 min) enhanced the activities of SpVc neurons (20/24) induced by both touch/pressure and pinch stimuli and also lowered the mechanical stimulation threshold (touch/pressure). Spontaneous discharges in these neurons (20/24) were significantly increased after bicuculline application. Eighteen out of 24 SpVc neurons showed signs of expansion of the receptive field size after iontophoretic application of bicuculline. These changes showed a current-dependent manner and were reversed in approximately 15-20 min. Iontophoretic application of the GABA(A) agonist muscimol induced a current-related inhibition of neuronal activity elicited by touch/pressure and pinch stimuli as well as a decrease in the size of receptive fields. The facilitation of evoked responses and receptive field expansion of SpVc neuron induced by bicuculline application were blocked by coapplication of muscimol (50 nA, 5 min). These results suggest that a local mechanism acting via GABA(A) receptors normally exerts a tonic inhibition of mechanoreceptive transmission in the trigeminal spinal nucleus neurons and this effect may limit responsiveness and size of receptive fields.

Multiple Components of Ipsilaterally Evoked Inhibition in the Inferior Colliculus

The central nucleus of the inferior colliculus (ICc) receives a large number of convergent inputs that are both excitatory and inhibitory. Although excitatory inputs typically are evoked by stimulation of the contralateral ear, inhibitory inputs can be recruited by either ear. Here we evaluate ipsilaterally evoked inhibition in single ICc cells in awake Mexican free-tailed bats. The principal question we addressed concerns the degree to which ipsilateral inhibition at the ICc suppresses contralaterally evoked discharges and thus creates the excitatory-inhibitory (EI) properties of ICc neurons. To study ipsilaterally evoked inhibition, we iontophoretically applied excitatory neurotransmitters and visualized the ipsilateral inhibition as a gap in the carpet of background activity evoked by the transmitters. Ipsilateral inhibition was seen in 86% of ICc cells. The inhibition in most cells had both glycinergic and GABAergic components that could be blocked by the iontophoretic application of bicuculline and strychnine. In 80% of the cells that were inhibited, the ipsilateral inhibition and contralateral excitation were temporally coincident. In many of these cells, the ipsilateral inhibition suppressed contralateral discharges and thus generated the cell's EI property in the ICc. In other cells, the ipsilateral inhibition was coincident with the initial portion of the excitation, but the inhibition was only 2-4 ms in duration and suppressed only the first few contralaterally evoked discharges. The suppression was so slight that it often could not be detected as a decrease in the spike count generated by increasing ipsilateral intensities. Twenty percent of the cells that expressed inhibition, however, had inhibitory latencies that were longer than the excitatory latencies. In these neurons, the inhibition arrived too late to suppress most or any of the discharges. Finally, in the majority of cells, the ipsilateral inhibition persisted for tens of milliseconds beyond the duration of the signal that evoked it. Thus ipsilateral inhibition has multiple components and one or more of these components are typically evoked in ICc neurons by sound received at the ipsilateral ear.

GABA-mediated representation of temporal information in rat barrel cortex.

Temporal sequences of inputs to the rat whiskers are thought to be important to recognize the environment of the rat. In this study, we applied combined stimulations to neighboring whiskers D1 and D2, and the cortical activities evoked in the rat barrel cortex were measured using the intrinsic optical imaging technique. The timing of stimulation to neighboring whiskers affected the evoked cortical activities: the cortical activity evoked by in-phase stimulation to D1 and D2 was significantly stronger than that evoked by out-of-phase stimulation. In order to elucidate the mechanism underlying this phenomenon, the effect of blockade of cortical inhibitory circuits was examined. Iontophoretic application of bicuculline or saclofen (GABA-A or GABA-B antagonist) increased the evoked cortical activities and diminished the difference in activities obtained with in-phase and anti-phase stimulation. These results suggest that local inhibitory circuits play a critical role in coding temporal information of whisker stimulation.

Analysis of the role of inhibition in shaping responses to sinusoidally amplitude-modulated signals in the auditory system

Neurons in the inferior colliculus (IC) typically respond with phase-locked discharges to low rates of sinusoidal amplitude modulated (SAM) signals and fail to phase-lock to higher SAM rates. The hypothesis that these properties are shaped by the integration of phase-locked excitation and inhibition, as they are in lower nuclei, was tested. Responses were recorded from IC neurons evoked by SAM signals before and during the iontophoretic application of bicuculline, a competitive antagonist for GABAA receptors, strychnine, a competitive antagonist for glycine receptors, and the GABAB receptor blocker, phaclofen. The hypothesis that inhibition shapes responses to SAM signals in the IC was not confirmed. In more than 90% of the ICc neurons tested, the range of SAM rates to which they phase-locked was unchanged after blocking inhibition with bicuculline, strychnine, or phaclofen, applied either individually or in combination. These results illustrate that the same response property, phase-locking restricted to low SAM rates, is formed in more than one way in the auditory brainstem. In lower nuclei, the mechanism is coincidence of phase-locked excitation and inhibition, whereas in IC the same response feature is formed by a different but unknown mechanism. [Work supported by NICD.]

Intrinsic and extrinsic connections of the rat central extended amygdala: an in vivo electrophysiological study of the central amygdaloid nucleus

Anatomical studies have shown that the central amygdaloid nucleus (CeA) is reciprocally connected with the lateral bed nucleus of the stria terminalis (BSTL), both structures being major components of the central extended amygdala. The CeA also receives projections from the insular cortex (InsCx) and the paraventricular thalamic nucleus (PVT). Extracellular unit activity was recorded from neurons in the lateral CeA (CeL) in urethane anaesthetized rats and their responses were studied after electrical stimulation of the BSTL, InsCx and PVT. The spontaneous activity of CeL neurons was low (1.69 spikes/s) and 40% of recorded cells were silent. The iontophoretic application of the GABA A antagonist, bicuculline, increased the firing rate of 20% of neurons. The BSTL stimulation induced an antidromic response in 33% of the tested cells. Orthodromic responses were obtained from 83% (BSTL stimulation), 70% (InsCx stimulation) and 85% (PVT stimulation) of tested cells, some of which responded to both BSTL and InsCx or PVT stimulations. Orthodromic responses mostly consisted in 1–3 orthodromic spikes followed by an inhibition. During iontophoretic application of bicuculline, stimulation induced additional short latency orthodromic spikes, even in cells that were previously unresponsive. However, the duration of the inhibition was never reduced. These results indicate that GABAergic neurotransmission may play a dominant role in both spontaneous and evoked electrical activities in the CeL, probably mediated by local circuit cells involved in a feed-forward inhibition. This organization, along with the reciprocal connections between the CeL and the BSTL, is considered in the context of the extended amygdala.

Electrophysiological evidence that noradrenergic neurons of the rat locus coeruleus are tonically inhibited by GABA during sleep.

It is well known that noradrenergic locus coeruleus (LC) neurons decrease their activity during slow wave sleep (SWS) and are virtually quiescent during paradoxical sleep (PS). It has been proposed that a GABAergic input could be directly responsible for this sleep-dependent neuronal inactivation. To test this hypothesis, we used a new method combining polygraphic recordings, microiontophoresis and single-unit extracellular recordings in unanaesthetized head-restrained rats. We found that iontophoretic application of bicuculline, a specific GABA(A)-receptor antagonist, during PS and SWS restore a tonic firing in the LC noradrenergic neurons. We further observed that the application of bicuculline during wakefulness (W) induced an increase of the discharge rate. Of particular importance for the interpretation of these results, using the microdialysis technique, Nitz and Siegel (Neuroscience, 1997; 78: 795) recently found an increase of the GABA release in the cat LC during SWS and PS as compared with waking values. Based on these and our results, we therefore propose that during W, the LC cells are under a GABAergic inhibitory tone which progressively increases at the entrance and during SWS and PS and is responsible for the inactivation of these neurons during these states.

Medullospinal vasomotor neurones mediate hypotension from stimulation of prefrontal cortex

Electrical stimulation of the prefrontal cortex in anaesthetised, paralysed rats evokes transient hypotension. In this study we have endeavoured to determine whether this evoked response is mediated by the spinal cord-projecting vasomotor neurones of the rostroventrolateral medulla (RVL). The responses of RVL-spinal vasomotor neurones to electrical stimulation of the prefrontal cortex caused a period of inhibition of the neuronal activity in the majority of cases (11 out of 13 neurones tested, 85%) and a short period of excitation in the remaining 2 neurones (15%). The prefrontal cortex-evoked inhibition of RVL-spinal vasomotor neurones was eliminated by iontophoretic application of bicuculline, a GABAa receptor antagonist, to the RVL-spinal vasomotor neurones. Microinjection of 50 nl of bicuculline methiodide into the same area of the RVL where the neurones have been identified converted the prefrontal-evoked hypotension into a vasopressor response. These findings indicate that the hypotension evoked by stimulating the prefrontal cortex is mediated by GABAergic inhibition of the RVL-spinal vasomotor neurones.

Ethanol potentiates the effect of γ-aminobutyric acid on medial vestibular nucleus neurons responding to horizontal rotation

Electrophysiological studies were performed to determine whether or not ethanol potentiates the inhibitory effects of γ-aminobutylic acid (GABA) on medial vestibular nucleus (MVN) neurons responding to horizontal sinusoidal rotation using α-chloralose anesthetized cats. The MVN neurons were classified into types I, II, III and IV neurons according to the responses to the horizontal rotation of the animal placed on the turntable in directions ipsilateral and contralateral to the recording site. In addition, the effects of ethanol and GABA on type I neurons were also examined. Micro-osmotic application of ethanol up to 100 nA did not affect the spontaneous firing or the rotation-induced increase in firing of type I neurons. However, the inhibitory effects of GABA up to 50 nA on the rotation-induced increase in firing were potentiated during simultaneous application of ethanol up to 100 nA. This potentiated inhibition was blocked by iontophoretic application of bicuculline (25–150 nA) and picrotoxin (45–150 nA). These results suggest that ethanol potentiates the inhibitory effects of GABA on MVN type I neurons by acting on the GABA receptor and/or receptor-coupled chloride ion channel.

The influence of GABAergic inhibitory processes on the receptive field structure of X and Y cells in cat dorsal lateral geniculate nucleus (dLGN)

Visually elicited inhibitory processes, underlying the receptive field structure of cells in layers A and A1 of the cat dorsal lateral geniculate nucleus (dLGN), have been examined by a combination of visual neurophysiological and iontophoretic techniques. Discrete visual stimulation of both centre and surround mechanisms, produced a powerful suppression of the elevated background discharge levels induced by iontophoretic application of an excitatory amino acid. These observations are consistent with the activation of a postsynaptic inhibitory input, a view supported by the fact that the suppressive effects were blocked by iontophoretic application of bicuculline, an antagonist of GABA, a putative inhibitory transmitter in the dLGN. These inhibitory effects were always elicited by the opposite phase of a flashed stimulus to that eliciting responses associated with the receptive field region. That is ‘on’ inhibitory effects were elicited from ‘off’ excitatory regions and ‘off’ inhibitory effects from ‘on’ excitatory regions. Plotting the responses of dLGN cells to flashed stimuli of increasing diameter, before and during iontophoretic application of bicuculline, revealed a marked reduction of the surround antagonism of centre response in the presence of the drug. During bicuculline application, surround antagonism of centre responses was at a level associated with that seen in retinal ganglion cells. Annular stimuli of internal and external diameter selected to be just outside the centre-surround border, insofar as they gave pure surround responses, were observed in the presence of bicuculline to elicit strong centre responses, as well as surround responses. These observations indicate that GABAergic inhibitory processes generate the enhanced centre-surround antagonism associated with dLGN cells and serve to increase the contrast between the two sets of mechanisms at the centre-surround border. The present conclusions apply equally to ‘X’ and ‘Y’ cells.

Actions of GABA, glycine, methionine-enkephalin and β-endorphin compared with electrical stimulation of nucleus raphe magnus on responses evoked by tooth pulp stimulation in the medial reticular formation in the cat

In decerebrate, cerebellectomised cats, a comparison was made between the effects of electrical stimulation in nucleus raphe magnus (NRM) and iontophoretic application of GABA, glycine, met-enkephalin and β-endorphin on the responses of neurones in the medial brain stem reticular formation to tooth pulp stimulation. NRM stimulation, GABA, glycine and enkephalin produced a short lasting inhibition of tooth pulp evoked responses whilst the time course of the inhibition produced by β-endorphin was much slower, often lasting up to 1 h following a 3–7 min ejection period. The effects of GABA and glycine could be antagonised by iontophoresis of bicuculline and strychnine respectively whilst intravenous injection of naloxone antagonised the inhibition induced by the opioid peptides. In most neurones tested, inhibition of tooth pulp evoked responses by NRM stimulation was blocked by iontophoretic application of bicuculline but not by strychnine or naloxone (i.v.). We conclude that GABA may act as a transmitter which mediates the inhibitory effects of NRM on the responses of reticular neurones to tooth pulp stimulation. Thus GABA may be involved in stimulation produced analgesia.

ネコ前庭神経外側核への中枢内入力系に関するＨＲＰおよび電気生理学的研究 特にオリーブ核‐前庭神経外側核系について

Central projections to the lateral vestibular nucleus (LVN) in cats were examined using a retrograde transport of horseradish peroxidase (HRP). Furthermore, electrophysiological studies were performed to elucidate the influence of the inferior olivary nucleus (IO) on the LVN neuron and possible neurotransmitters involved in the transmission from the IO to the LVN using the microiontophoretic technique. When HRP was microiontophoretically applied to the immediate vicinity of the LVN neuron, which was monosynaptically activated by vestibular nerve stimulation, HRP-labeled cells were found in the following areas: bilateral fastigial, bilateral dentate and ipsilateral interpositus nuclei of cerebellum; bilateral medial, bilateral descending and contralateral lateral vestibular nuclei; bilateral gigantocellular and ipsilateral lateral reticular nuclei; and contralateral dorsal cap and β nucleus of the IO. HRP-labeled Purkinje cells were observed in the ipsilateral cerebellar nodulus, ligula and flocculus. Effects of IO stimulation were examined on 168 LVN neurons monosynaptically elicited by vestibular nerve stimulation using decerebellate cats anesthetized with α-chloralose. Forty-three neurons were monosynaptically activated by IO stimulation and excitatory responses were dose-dependently inhibited with iontophoretic application of atropine, an anticholinergic drug. The conditioning stimulus to the IO preceding the test stimulus to the vestibular nerve inhibited the orthodromic spike upon the test stimulation in 22 neurons and the inhibition was antagonized with iontophoretic application of bicuculline, a GABA antagonist. In 9 LVN neurons, IO stimulation produced an antidromic spike. Histological examination showed that excitatory and/or inhibitory effects on the LVN neurons were observed when the stimulus was applied to the dorsal cap and/or β nucleus of the contralateral IO. These results suggest that the LVN neurons monosynaptically activated by vestibular nerve stimulation receive both excitatory input mediated by acetylcholine and inhibitory effect mediated by GABA from the contralateral dorsal cap and β nucleus of the IO.

Responses of somatosensory cortical neurons to inhibitory amino acids during topical and iontophoretic application of epileptogenic agents

Single unit activity in cat primary somatosensory cortex (layers IV–VI) with contralateral forelimb receptive fields was recorded extracellularly via compound multi-barrelled micropipettes with simultaneous iontophoresis of amino acids. Units exhibited inhibitory responses to γ-aminobutyric acid (GABA), β-alanine (ALA), and l-glycine (GLY). The order of potency was GABA > ALA > GLY. Excitatory responses to d,l-homocysteic acid (HC) and l-glutamate (GLU) were observed. HC was more potent than GLU. In topical penicillin, bicuculline, or strychnine foci units, at the depth studied (1–2 mm), had HC-induced interburst activity which was normally responsive to GABA, ALA or GLY. This occurred despite obvious epileptic involvement of the unit in a bursting firing pattern associated with paroxysmal electrocorticogram (ECoG) discharges. Unit bursts proved to be completely resistant to the exogenous inhibitory amino acids applied by iontophoresis. Iontophoretic application of bicuculline (100 nA) antagonized neuronal responses to GABA and ALA without effect on GLY. Strychnine (100 nA) antagonized responses to GLY and ALA, without effect on GABA. A comparison of topical and iontophoretic results indicated failure of topical epileptogenic agents to consistently diffuse in adequate concentration into deeper cortical layers (IV–VI) to produce characteristic receptor antagonism. The iontophoretic application technique was consequently selected as the most appropriate method for further study of the effects of penicillin iontophoresis on responses of deep cortical neurons to amino acids.

A comparison of the inhibitory effects of taurine and GABA on identified Purkinje cells and other neurons in the cerebellar cortex of the rat

The microiontophoretic application of taurine and GABA was studied in the cerebellar cortex of the rat. Both taurine and GABA produced a dose-dependent depression of spike frequency of cerebellar neurons. GABA (2–42 nA, mean 27 nA) induced an inhibition of spike discharge on all 138 cells tested, including 29 Purkinje cells. Taurine (60–200 nA, mean 108 nA) induced an inhibition of spike discharge on 93 of the 106 cerebellar neurons tested, including inhibition on 22 of 25 Purkinje cells. Iontophoretic application of bicuculline and picrotoxin antagonized the inhibitory effects of both GABA and taurine on Purkinje cells as well as on cerebellar neurons in general. Strychnine did not antagonize the inhibition of either GABA or taurine. Simultaneous application of taurine and GABA produced a synergistic inhibitory effect on the firing rate of Purkinje cells. Taurine, in contrast to GABA, appeared to be more depressant when applied in the Purkinje cell dendritic zone than when applied near the soma. The data are discussed in terms of taurine functioning as a neurotransmitter in the cerebellum of the rat and having receptor sites distinct from those for GABA.

Inhibitory processes underlying the directional specificity of simple, complex and hypercomplex cells in the cat's visual cortex

1. The iontophoretic application of bicuculline, an antagonist of GABA, the putative inhibitory transmitter in the visual cortex, has been used to examine the contribution of post-synaptic inhibitory processes to the directional selectivity of simple, complex and hypercomplex cells in the cat's striate cortex.2. The directional selectivity of simple cells was significantly reduced or eliminated during the iontophoretic application of bicuculline. This supports the view that the selectivity is derived from the action of a GABA-mediated post-synaptic inhibitory input modifying their response to a non-directionally specific excitatory input.3. Complex cells were subdivided into three categories on the basis of the action of iontophoretically applied bicuculline on their directional selectivity, receptive field characteristics and distribution in terms of cortical layer. They are referred to as type ;1', ;2' and ;3' complex cells.4. The directional specificity of type ;1' complex cells was eliminated during the iontophoretic application of bicuculline. It seems likely, therefore, that they receive a non-directionally specific excitatory input and that, as for simple cells, the directional specificity derives from the action of a GABA-mediated post-synaptic inhibitory input. No type ;1' complex cells were recorded below layer IV.5. The directional specificity of type ;2' complex cells was unaffected by the iontophoretic application of bicuculline, despite increases in response magnitude, a block of the action of iontophoretically applied GABA and, in some cases, changes in other receptive field properties. It is suggested that these cells receive a directionally specific excitatory input. The type ;2' complex cells were found both superficial and deep to layer IV with the majority in layer V.6. Type ;3' complex cells appear to have very similar receptive field properties to those of the cells described by other workers as projecting to the superior colliculus. They were found predominantly in layer V. Their directional specificity was not eliminated by the iontophoretic application of bicuculline. However, they exhibited a powerful suppression of the resting discharge in response to stimulus motion in the non-preferred direction. Iontophoretic application of ammonium ions revealed a small excitatory response in place of the suppression. It appears from these observations that the directional specificity of the type ;3' complex cells could be determined, at least in part, by an inhibitory process which is not GABA-mediated.7. The directional specificity of hypercomplex cells found in layers II and III was unaffected by the iontophoretic application of bicuculline, and they showed no suppression of their background discharge level in response to stimulus motion in the non-preferred direction. This evidence is consistent with the view that they receive a directionally specific excitatory input.