GABA Injection Research Articles

Embryonic opioid exposure impairs inhibitory transmission of striatum in day-old chicks.

Studies of humans, mammalian animals, and chicks reveal that embryonic opioid exposure (EOE) changes the response to pharmacological rewards in postnatal individuals, which may be an outcome of permanent alterations to neural systems. However, the mechanism behind this alteration remains unclear. GABA transmitter has a trophic effect on early GABAergic neuronal development, and EOE decreases GABA concentration in developing brains. Here, we determined whether the development of inhibitory transmission was affected by EOE and whether altered GABA release was the underlying mechanism. We revealed that morphine administration in the early but not the late embryonic period decreased inhibitory transmission in the striatum of chicks. Meanwhile, day-old chicks with early embryonic morphine exposure showed increased psychomotor activity after acute morphine injection compared with saline-exposed chicks. Furthermore, GABA injection in the chick embryo following morphine administration mitigated damage to GABA transmission and recovered the behavioral response to acute morphine injection in chicks. Collectively, our findings suggest that abnormal GABA release in the early embryonic period induced by opioid exposure is attributable to functional and structural developments of the GABA synapse, and that the dysfunction of striatal GABA transmission may be linked to enhanced psychomotor response during initial drug exposure in postnatal life.

In Ovo Injection of GABA Can Help Body Weight Gain at Hatch, Increase Chick Weight to Egg Weight Ratio, and Improve Broiler Heat Resistance.

Simple SummaryHeat stress is a vital issue that causes severe losses to the poultry industry. A partly developed thermoregulatory mechanism during the embryonic phase is emphasized to manipulate embryos for achieving thermotolerance during rearing. The present study was conducted firstly to standardize the dosage for an in ovo manipulation, and the selective dose was used to evaluate its effects on early-age heat-stressed (HS) broilers. HS induces cholesterol while an antioxidant acts as a first line of defense under stress. However, 5% GABA supplementation had a higher hatchling weight and chick weight to egg weight ratio (CWEWR). We selected a 10% GABA dosage for HS studies due to its higher antioxidants and lower cholesterol values in hatchlings. In ovo, 10% GABA supplementation significantly increased total antioxidant capacity and reduced malondialdehyde levels, hepatic mRNA levels of HSP70, FAS, and L-FABP in broilers when subjected to HS (38 ± 1 °C; 3 h) at ten days of age. This indicates that an in ovo GABA injection improves CWEWR and antioxidant status at hatch, and creates thermotolerance by increasing antioxidant production and downregulating the expression of HSP70 and fatty acid metabolism genes in HS chicks.The aim of this study was to explore the outcomes of an in ovo GABA injection in broilers challenged with HS. In Experiment 1, 210 Arbor Acres eggs were allocated to five treatments: no-injection, and in ovo injection of 0.6 mL of 0%, 5%, 10%, or 20% of GABA. Hatchling weight and CWEWR were significantly increased in the 5% GABA group. In ovo, injection of 10% GABA solution caused a significant decrease in plasma cholesterol and increased plasma total antioxidant capacity of hatchlings. Experiment 2 was conducted with 126 fertile Arbor Acres eggs distributed into one of two groups. At 17.5 days of incubation, one received no injection, and the other was fed 0.6 mL of 10% GABA. On day 10, one subgroup (4 replicates * 3 birds) from each treatment was submitted to HS (38 ± 1 °C for 3 h) while the other was kept at a thermoneutral temperature (29 ± 1 °C). An in ovo injection of GABA significantly increased total antioxidant capacity, but reduced malondialdehyde levels, hepatic mRNA levels of HSP70, FAS, and L-FABP with HS. In conclusion, an in ovo GABA injection improves CWEWR and antioxidant status at hatch, and enhances antioxidant status while downregulating the expression of HSP70 and fatty acid metabolism-related genes in young chicks under HS.

Gamma-aminobutyric acid regulates glucose homeostasis and enhances the hepatopancreas health of juvenile Chinese mitten crab (Eriocheir sinensis) under fasting stress

The ability of immune defense and resistance to physiological stress is crucial to animal health and survival. This study investigated the regulation of γ-aminobutyric acid (GABA) on metabolic homeostasis and its enhancement of hepatopancreas health in juvenile Chinese mitten crab (Eriocheir sinensis) under food deprivation. Juvenile crabs of 400 individuals were divided into four treatment groups: a control group without injection, and injections with a phosphate-buffered saline solution, 100 μmol GABA/mL and 1000 μmol GABA/mL, respectively. Hypoglycemia was induced by fasting, whereas the GABA treatment regulated hemolymph glucose homeostasis. The quantitative real-time PCR (qRT-PCR) results showed that the GABA treatment significantly up-regulated the mRNA expression levels of crustacean hyperglycemic hormone (CHH) and pyruvate kinase (PK). In contrast, the expression of E. sinensis insulin-like peptide (EsILP) was significantly down-regulated in the cranial ganglia, thoracic ganglia and hepatopancreas. Moreover, acid phosphatase (ACP), alkaline phosphatase (AKP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were significantly increased in the hepatopancreas by the GABA treatment. Furthermore, the hemocyanin content in serum was significantly increased with the GABA injection, and the glutathione (GSH) content, total superoxide dismutase (T-SOD) activity and catalase (CAT) activity in the hepatopancreas showed a similar increasing trend with the dose elevation of GABA. Therefore, these results indicate that GABA can effectively maintain the hemolymph glucose homeostasis by regulating the levels of glucose metabolism-related hormones and key enzymes to promote the degradation and utilization of hepatopancreas glycogen. Meanwhile, GABA can improve the hepatopancreas function and immune status of juvenile E. sinensis under fasting stress. The treatment with GABA may provide a clue to guide health management in crab farming.

Modulation of brain function by targeted delivery of GABA through the disrupted blood-brain barrier

The technology of transcranial focused ultrasound (FUS) enables a novel approach to neuromodulation, a tool for selective manipulation of brain function to be used in neurobiology research and with potential applications in clinical treatment. The method uses transcranial focused ultrasound to non-invasively open the blood-brain barrier (BBB) in a localized region such that a systemically injected neurotransmitter chemical can be delivered to the targeted brain site. The approach modulates the chemical signaling that occurs in and between neurons, making it complimentary to most other neuromodulation techniques that affect the electrical properties of neuronal activity. Here, we report delivering the inhibitory neurotransmitter GABA to the right somatosensory cortex of the rat brain during bilateral hind paw electrical stimulation and measure the inhibition of activation using functional MRI (fMRI). In a 2 × 2 factorial design, we evaluated conditions of BBB Closed vs BBB Open and No GABA vs GABA. Results from fMRI measurements of the blood oxygen level-dependent (BOLD) signal show: 1) intravenous GABA injection without FUS-mediated BBB opening does not have an effect on the BOLD response; 2) FUS-mediated BBB opening alone significantly alters the BOLD signal response to the stimulus, both in amplitude and shape of the time course; 3) the combination of FUS-mediated BBB opening and GABA injection further reduces the peak amplitude and spatial extent of the BOLD signal response to the stimulus. The data support the thesis that FUS-mediated opening of the BBB can be used to achieve non-invasive delivery of neuroactive substances for targeted manipulation of brain function.

Excitatory and inhibitory influence of exogenous neurotransmitters on reproduction in female rats

Neurotransmitters are mediators inside the nervous system responsible for transmitting neural-neural or neural-organs signals. Several neural studies have tried to unveil the role of such mediators whose action extended outside the nervous system such as immune, digestive, circulatory and reproductive systems. The present study aimed to investigate the role of the excitatory-glutamate and inhibitory-GABA transmitters in female rats reproduction including their effects on gonadotropins; luteinizing hormone (LH) and follicle stimulating hormone (FSH) and the sex steroids; estrogen (E2) and progesterone (P4) during the estrous cycle as well. Furthermore, the responsive changes on the ovarian tissue were also studied. Synthetic glutamate and GABA were injected intraperitoneally (ip) in those animals throughout four successive estrous cycles. Interestingly, the ip injections of glutamate increased the levels of LH, E2 and P4 but decreased those of FSH significantly. However, the ip injections of GABA significantly decreased the levels of LH in the 4th cycles and FSH throughout treatment period while it increased the levels of E2 and P4. All changes occurred in those reproductive hormones caused by glutamate has been recovered after cessation of glutamate and GABA injection except FSH, including; the 5th, 6th and 7th cycles. Regarding to histopathological examination, ovaries of treated rats showed deleterious changes. The glutamate-treated rats ovaries showed atrophy of the primary follicles with degenerative changes in those secondary and tertiary follicles with obvious degeneration in the granulosa cell layer with vacuolated cytoplasm. On the other hand, those received GABA showed degeneration of the oocytes with congestion of blood vessels supplying the corpora lutea (CL) associated with endothelial changes. The histopathological changes in CL have been improved after glutamate cessation while not changed after GABA cessation.

Effects of GABA microinjection into dorsal raphe nucleus on behavior and activity of lateral habenular neurons in mice

The dorsal raphe nucleus (DRN) is a key site for 5-hydroxytryptamine (5-HT) synthesis and release. DRN dysfunction has been implicated in several stress-related disorders, including depression and anxiety. The lateral habenular nucleus (LHb) has been shown to inhibit the activity of DRN 5-HT neurons, and thus the LHb-DRN pathway plays an important role in the pathogenesis of depression. Although it is known that the LHb also receives the projection from the 5-HT neuron in the DRN, whether 5-HT neurons in the DRN can influence activity of the LHb in vivo and whether this effect is related to the induced behavioral changes have not been investigated. In the current study, we determined how injecting γ-aminobutyric acid (GABA) into the DRN to inhibit 5-HT neurons affected behavior and the changes in the activity of LHb neurons in mice. We found that GABA injection into the DRN induced depression-like behavior in mice, as indicated by increased immobility time, and decreased climbing time in the forced swimming test and the tail suspension test, decreased time spent in the center and total distance moved in the open field test. Using extracellular single unit recording, we showed that the firing rate of LHb neurons decreased after GABA microinjection into the DRN. Further, c-Fos expression in LHb neurons was inhibited. Together our results indicate that inhibition of DRN 5-HT neurons can cause decreased LHb activity and depression-like behavior in mice, however this depression-like behavior could be independent of the LHb activity. The observed decrease in LHb activity is probably due to the presence of a negative feedback loop between the DRN and the LHb, which may play a role in maintaining emotional homeostasis.

A Potential Magnetic Resonance Imaging Technique Based on Chemical Exchange Saturation Transfer for In Vivo γ-Aminobutyric Acid Imaging

PurposeWe developed a novel magnetic resonance imaging (MRI) technique based on chemical exchange saturation transfer (CEST) for GABA imaging and investigated the concentration-dependent CEST effect ofGABA in a rat model of brain tumor with blood—brain barrier (BBB) disruption.Materials and MethodsAll MRI studies were performed using a 7.0-T Agilent MRI scanner. Z-spectra for GABA were acquired at 7.0 T, 37°C, and a pH of 7.0 using varying B1 amplitudes. CEST images of phantoms with different concentrations of GABA solutions (pH, 7.0) and other metabolites (glutamine, myoinositol, creatinine, and choline) were collected to investigate the concentration-dependent CEST effect of GABA and the potential contribution from other brain metabolites. CEST maps for GABA in rat brains with tumors were collected at baseline and 50 min, 1.5 h, and 2.0 h after the injection of GABA solution.ResultsThe CEST effect of GABA was observed at approximately 2.75 parts per million(ppm) downfield from bulk water, and this effect increased with an increase in the B1 amplitude and remained steady after the B1 amplitude reached 6.0 μT (255 Hz). The CEST effect of GABA was proportional to the GABA concentration in vitro. CEST imaging of GABA in a rat brain with a tumor and compromised BBB showed a gradual increase in the CEST effect after GABA injection.ConclusionThe findings of this study demonstrate the feasibility and potential of CEST MRI with the optimal B1 amplitude, which exhibits excellent spatial and temporal resolutions, to map changes in GABA.

GABA-induced inactivation of Cebus apella V2 neurons: effects on orientation tuning and direction selectivity

We investigated the GABA-induced inactivation of V2 neurons and terminals on the receptive field properties of this area in an anesthetized and paralyzed Cebus apella monkey. Extracellular single-unit activity was recorded using tungsten microelectrodes in a monkey before and after pressure-injection of a 0.25 or 0.5 M GABA solution. The visual stimulus consisted of a bar moving in 8 possible directions. In total, 24 V2 neurons were studied before and after blocker injections in 4 experimental sessions following GABA injection into area V2. A group of 10 neurons were studied over a short period. An additional 6 neurons were investigated over a long period after the GABA injection. A third group of 8 neurons were studied over a very long period. Overall, these 24 neurons displayed an early (1-20 min) significant general decrease in excitability with concomitant changes in orientation or direction selectivity. GABA inactivation in area V2 produced robust inhibition in 80% and a significant change in directional selectivity in 60% of the neurons examined. These GABA projections are capable of modulating not only levels of spontaneous and driven activity of V2 neurons but also receptive field properties such as direction selectivity.

GABA inactivation of visual area MT modifies the responsiveness and direction selectivity of V2 neurons in Cebus monkeys

We investigated the contribution of the projections from area MT to the receptive field properties of cells in visual area V2 in anesthetized and paralyzed Cebus apella monkeys. We recorded extracellular single-unit activity using tungsten microelectrodes in three monkeys before and after pressure injection of a 0.25-mol/l GABA solution. The visual stimulus consisted of a single bar moving in one of eight directions. In total, 72 V2 neurons were studied in 18 sessions of GABA injection into area MT. A group of 22 neurons was investigated over a shorter period of time ranging from 15 to 60 min, during which the activity did not return to baseline levels. The remaining 50 neurons were studied over a period of at least 2 h, and no statistical difference was observed in the neuronal response before and long after GABA inactivation. The effects on these 50 neurons consisted of an early (1-20 min) significant general decrease in excitability with changes in either orientation or direction selectivity. The differential decrease in excitability resulted in an intermediate improvement (20-40 min) of the signal-to-noise ratio for the stimulus-driven activity. The inactivation depended on the quantity of GABA injected into area MT and persisted for a period of 2 h. The GABA inactivation in area MT produced inhibition of most cells (72%) and a significant change of direction tuning in the majority (56%) of V2 neurons. Both increases and also decreases in the direction tuning of V2 neurons were observed. These feedback projections are capable of modulating not only the levels of spontaneous and driven activity of V2 neurons but also the V2 receptive field properties, such as direction selectivity.

Interruption of pacemaker signals is mediated by GABAergic inhibition of the pacemaker nucleus in the African electric fish Gymnarchus niloticus

The wave-type African weakly electric fish Gymnarchus niloticus produces electric organ discharges (EODs) from an electric organ in the tail that is driven by a pacemaker complex in the medulla, which consists of a pacemaker nucleus, two lateral relay nuclei and a medial relay nucleus. The prepacemaker nucleus (PPn) in the area of the dorsal posterior nucleus of the thalamus projects exclusively to the pacemaker nucleus and is responsible for EOD interruption behavior. The goal of the present study is to test the existence of inhibition of the pacemaker nucleus by the PPn. Immunohistochemical results showed clear anti-GABA immunoreactive labeling of fibers and terminals in the pacemaker nucleus, but no apparent anti-glycine immunoreactivity anywhere in the pacemaker complex. GABA injection into the pacemaker nucleus could induce EOD interruptions that are comparable to the interruptions induced by glutamate injection into the PPn. Application of the GABA(A) receptor blocker bicuculline methiodide reversibly eliminated the effects of stimulation of the PPn. Thus the EOD interruption behavior in Gymnarchus is mediated through GABAergic inhibition of the pacemaker nucleus by the PPn.

Control of oro-facio-lingual movements by the substantia nigra pars reticulata: High-frequency electrical microstimulation and GABA microinjection findings in rats

To provide direct evidence for substantia nigra pars reticulata (SNr) control of oro-facio-lingual muscle activity, high-frequency electrical microstimulation (mainly trains of 20, 333-Hz cathodal pulses at 40–60μA) and GABA microinjection (1–5μl of 10mM GABA in saline) were carried out using a three-barreled microelectrode at the same SNr site in lightly anesthetized, chronically decorticated rats ( n=39). Decortication eliminated the possibility that SNr microstimulation might activate corticofugal fibers descending in the adjoining cerebral peduncle. When the most ventral layer of the SNr was approached, high-amplitude electromyographic (EMG) activity of up to 6 mV with a distinctive waveform appeared synchronously with electrical stimuli in the anterior digastric, masseter, genioglossus, and levator labii superioris muscles. This EMG activity was evoked bilaterally, with an ipsilateral predominance. Eye movements, mostly rotation of the eyeball vertically down in the orbit, were noted. Infrequent blinking was also noted. Histologic examination localized the effector site to the middle third of the mediolateral extent of the caudal SNr corresponding to between 5.8mm (level of the oculomotor nerve) and 6.5mm (caudal end of the SNr) caudal to bregma; and to the ventralmost peripeduncular region of the SNr corresponding to 7.7mm to 8.0mm beneath the cortical surface. We referred to this site as the substantia nigra pars reticulata oro-facio-lingual (SNr-ofl) region. GABA injection produced tonic EMG discharge with consistent amplitude in all of the four muscles studied. The GABA effect was negated by a preceding microinjection of the GABA-A receptor antagonist bicuculline, whereas saline control injection had no effect. Changes in amplitude of evoked EMG activity according to location of the stimulating microelectrode reflected somatotopic organization of the SNr-ofl region. This extremely localized electrical and receptor microstimulation in the SNr produced synchronized powerful contraction of jaw, tongue, and facial muscles with different neural innervation. These findings advance our understanding of the mechanisms of the SNr concerning oro-facio-lingual movements.

Effects of inactivation of the lateral pulvinar on response properties of second visual area cells in Cebus monkeys.

1. In the present study, we investigated the influence of the pulvinar nucleus upon response properties of single cells in the second visual area (V2) of Cebus monkeys. The method used consisted of the inactivation of a portion of the lateral pulvinar by GABA injections while studying the response properties of cells in V2 at the same visuotopic location as that of the inactivation. 2. After GABA injection in the pulvinar, most cells in V2 (67%) showed changes in spontaneous and/or stimulus-driven activities. Contrary to the effect found with inactivation of the striate cortex, which promotes a reduction in the response of V2 neurons, we found that the main effect of pulvinar inactivation was an increment in stimulus-driven responses of V2 cells (39% of units studied). A reduction of responses was observed in 27% of units. 3. A change in orientation and/or direction selectivity was found in 91% of cells after inactivation of the pulvinar. Most commonly, the orientation selectivity of a neuron was decreased during pulvinar inactivation. 4. The inactivation results indicate that the pulvinar projections have a modulatory effect on the activity of V2 cells.

GABAergic and glutamatergic inhibition of nonspiking local interneurons in the terminal abdominal ganglion of the crayfish

Nonspiking local interneurons in the terminal abdominal ganglion of the crayfish Procambarus clarkii receive inhibitory inputs from mainly glutamatergic spiking local interneurons and GABAergic nonspiking interneurons. In this study, the inhibitory responses of nonspiking interneurons to local application of glutamate and GABA into the neuropil were compared. Glutamate and GABA injection mediated the hyperpolarization of the nonspiking interneurons with an increase in membrane conductance. The glutamate-mediated membrane hyperpolarization was reversed by injection of 1 or 2 nA hyperpolarizing current. By contrast, more than 3 nA hyperpolarizing current was frequently necessary to reverse the GABA-mediated hyperpolarization. Bath application of a chloride channel blocker, 50 microM picrotoxin (PTX), reduced the glutamate-mediated hyperpolarization, but had no effect on the GABA-mediated hyperpolarization. The GABA-mediated hyperpolarization was not consistently affected by bath application of low chloride solution. These results suggest that the glutamate-mediated inhibition was related to the gating of a Cl(-) conductance, while the GABA-mediated inhibition was not. Electrical stimulation of sensory afferents innervating the exopodite elicited ipsps in uropod opener motor neurons. These sensory-evoked ipsps were also PTX-insensitive, suggesting GABAergic nonspiking interneurons could be the predominant premotor elements in organizing the uropod motor control system.

Influence of an abrupt increase in blood pressure on the blood–brain barrier permeability during acute hypertension and epileptic seizures

The interrelationship between the breakdown of the blood–brain barrier according to the Evans-blue passage and an abrupt increase in blood pressure (ΔP) was studied in rats subjected to adrenaline-induced acute hypertension and also pentylenetetrazol-induced seizures. Arterial blood pressure was increased by adrenaline, then immediately i.v. nifedipine was injected and subsequently decreased to the control value in the acute hypertensive group. Arterial blood pressure was increased by pentylenetetrazol, then immediately GABA (γ -aminobutiric acid) was injected and the blood pressure was decreased to the control value in the seizure group. The animals were divided into five groups. Group I: control; Group II: acute hypertension; Group III: acute hypertension + nifedipine; Group IV: seizure; Group V: seizure + GABA. The Evans-blue dye content was found to be 0.25 ± 0.01 mg% in the whole brain in the control animals, and 0.803 ± 0.1 mg% in the acute hypertensive group. This difference between these groups was found to be significant: P< 0.01. In the nifedipine group (Group III) the Evans-blue content was 0.30 ± 0.1 mg% in the whole brain; and there was no significant difference between control values and nifedipine-treated animals (P> 0.5). The Evans-blue content was 1.6 ± 0.2 mg% in the whole brain during seizure, and decreased to 0.36 ± 0.1 mg% after GABA injection was administered. There was also no significant difference between the control value and the GABA-treated animals (P> 0.5). These results have shown that an abrupt increase in blood pressure (ΔP) did not change the blood–brain barrier permeability in both acute hypertension and seizures.

Asymmetrical effect of GABA on the postural orientation in Clione.

The marine mollusk Clione limacina, when swimming, normally stabilizes the vertical body orientation by means of the gravitational tail reflexes. Horizontal swimming or swimming along inclined ascending trajectories is observed rarely. Here we report that GABA injection into intact Clione resulted in a change of the stabilized orientation and swimming with a tilt of approximately 45 degrees to the left. The analysis of modifications in the postural network underlying this effect was done with in vitro experiments. The CNS was isolated together with the statocysts. Spike discharges in the axons of two groups of motoneurons responsible for the left and right tail flexion, as well as in the axons of CPB3 interneurons mediating signals from the statocyst receptors to the motoneurons, were recorded extracellularly when the preparation was rotated in space. Normally the tail motoneurons of the left and right groups were activated with the contralateral tilt of the preparation. Under the effect of GABA, the gravitational responses in the right group of motoneurons and in the corresponding interneurons were dramatically reduced while the responses in the left group remained unchanged. The most likely site of the inhibitory GABA action is the interneurons mediating signals from the statocysts to the right group of tail motoneurons. The GABA-induced asymmetry of the left and right gravitational tail reflexes, observed in the in vitro experiments, is consistent with a change of the stabilized orientation caused by GABA in the intact Clione.

Influences of area 17 on neuronal activity of simple and complex cells of area 18 in cats

To understand the influence of the ascending path linking area 17 to area 18 of visual cortices, experiments were carried out in which a small neuronal population of area 17 was inactivated with GABA, while unitary responses were recorded in area 18. In the latter, cells are identified as belonging to the simple or complex family according to their firing pattern evoked in response to sine-wave gratings scrolling through the receptive fields. Anesthetized cats were prepared for single-cell recordings. In area 17, a GABA-containing pipette was placed in superficial layers in order to inactivate reversibly a small neuronal population. Prior to blockade, the orientation tuning curves were obtained in both areas and the difference in optimal orientation between areas 17 and 18 was recorded. In area 18, cells were classified as simple or complex. The strategy was to study the reaction of neurons in area 18 prior to, during and after area 17 depression. In most simple cells, whenever the difference in orientation was in the iso-range, that is when the difference in optimal orientations of the injected site (in area 17) and of the neuron in area 18 was less than 30°, the GABA application produced a decline of the evoked discharges, whereas GABA injection augmented the evoked firing rate when the difference was in the cross-range (>60°). In contrast to simple cells, GABA depression enhanced the responses in the majority of complex cells with like orientations in both areas. When the difference between recording sites was in the cross-range, then area 17 depression produced weaker evoked firing. A tangential penetration of the injecting pipette, allowing injection of different orientation sites while testing the same unit in area 18, revealed that the latter could react with an enhancement or a decline of the responses as the injecting pipette shifted from iso (or cross) to cross (or iso) disparity in optimal orientations between areas 17 and 18. These results suggest that the path connecting area 17 to area 18 may be functionally discriminated on the basis of the orientation domain and cell types. In addition, our data suggest that the ascending visual streams are required to generate orientation specificity in area 18.

Two types of identified ascending interneurons with distinct GABA receptors in the crayfish terminal abdominal ganglion.

More than half of the identified ascending interneurons originating in the terminal abdominal ganglion of the crayfish received inhibitory sensory inputs from hair afferents innervating the tailfan on the side contralateral to their main branches. Biochemical aspects of this transverse lateral inhibition of ascending interneurons were examined by the use of neurophysiological and pharmacological techniques. Local application of gamma-aminobutyric acid (GABA) and its agonist muscimol into the neuropil induced membrane hyperpolarization of identified ascending interneurons with an increase in membrane conductance. Because the reversal potential of inhibitory postsynaptic potential (IPSPs) in ascending interneurons elicited by the sensory stimulation and GABA injection was similar, and the sensory-stimulated IPSPs of the interneurons were blocked by GABA and muscimol application, this study strongly suggests a GABAergic nature for transverse lateral inhibition of ascending interneurons. According to the response to the GABAA antagonists bicuculline and picrotoxin, ascending interneurons were classified into two types, picrotoxin-sensitive and picrotoxin-insensitive interneurons. Identified ascending interneurons VE-1 and RO-4 showed a pharmacological profile similar to that of the classical GABAA receptor of the vertebrates. Bath application of both bicuculline and picrotoxin reversibly reduced the amplitudes of IPSPs. The other identified ascending interneurons CA-1, RO-1, and RO-2 were not affected significantly by the bath application of GABAA and GABAB antagonists, although bath application of low-chloride saline reversed the sensory-stimulated IPSPs. IPSPs of the picrotoxin-sensitive interneurons had a rather faster time course and shorter duration in comparison with those of the picrotoxin-insensitive interneurons.

Two-dimensional receptive-field organization in striate cortical neurons of the cat.

The two-dimensional organization of receptive fields (RFs) of 44 cells in the cat visual cortex and four cells from the cat LGN was measured by stimulation with either dots or bars of light. The light bars were presented in different positions and orientations centered on the RFs. The RFs found were arbitrarily divided into four general types: Punctate, resembling DOG filters (11%); those resembling Gabor filters (9%); elongate (36%); and multipeaked-type (44%). Elongate RFs, usually found in simple cells, could show more than one excitatory band or bifurcation of excitatory regions. Although regions inhibitory to a given stimulus transition (e.g. ON) often coincided with regions excitatory to the opposite transition (e.g. OFF), this was by no means the rule. Measurements were highly repeatable and stable over periods of at least 1 h. A comparison between measurements made with dots and with bars showed reasonable matches in about 40% of the cases. In general, bar-based measurements revealed larger RFs with more structure, especially with respect to inhibitory regions. Inactivation of lower cortical layers (V-VI) by local GABA injection was found to reduce sharpness of detail and to increase both receptive-field size and noise in upper layer cells, suggesting vertically organized RF mechanisms. Across the population, some cells bore close resemblance to theoretically proposed filters, while others had a complexity that was clearly not generalizable, to the extent that they seemed more suited to detection of specific structures. We would speculate that the broadly varying forms of cat cortical receptive fields result from developmental processes akin to those that form ocular-dominance columns, but on a smaller scale.

Excitatory drive from deep cerebellar neurons to the superior colliculus in the rat: an electrophysiological mapping study.

The cerebello-tectal projection arising from the interpositus nucleus was investigated electrophysiologically to test the hypothesis that the deep cerebellar nuclei constitute a source of tonic excitation in the superior colliculus. A total of 117 spontaneously active collicular neurons were recorded during GABA microinjection into 26 interpositus sites, where tonic single-cell deep cerebellar activity was also simultaneously recorded. GABA injection always led to suppression of interpositus activity, while in the colliculus a clear pattern of results emerged. 58% of superior colliculus cells showed no response to suppression of interpositus activity, 35% showed a frequency decrease and 7% showed a frequency increase. The majority of these responsive cells were found in a laterally located sheet of cells mainly restricted to the intermediate white layer, in close register with the known cells of origin of the predorsal bundle and completely overlapping the terminals of the nigrotectal pathway originating in dorsolateral substantia nigra pars reticulata. The implications of these results for cooperative theories of head movement control involving the superior colliculus, cerebellum and precerebellar nuclei are discussed.

Preferential Hindquarter Vasodilation in the Hypotension Induced by GABA Injection into the Cisterna Magna of Conscious Rats.

Injection of GABA into the cisterna magna of conscious rats induced a vasodilation in the hindquarter without significant change in the renal and superior mesenteric areas, when arterial pressure and heart rate markedly decreased. This circulatory change indicates that GABA decreased arterial pressure as an effect on the CNS, in particular, through a hindquarter resistance reduction, along with a bradycardia.