Inhibition of spinal interneuronal activity by repeated cutaneous stimulation: a possible substrate of flexor reflex habituation

The responses of interneurones, situated in the lumbar region of the rat spinal cord, to repeated cutaneous stimulation, were studied. The main purpose of this investigation was to attempt to determine the extent to which habituation of the flexor reflex might be explained on the basis of a progressive development of inhibition. Spontaneously active interneurones, which were inhibited by cutaneous stimuli, were investigated in detail. In rats whose spinal cords were intact, the period of inhibition was shown to increase with successive stimuli. This increase in inhibition was directly related to the intensity and frequency of stimulation, occurred more rapidly during a second series of stimuli and was antagonized by strychnine. In spinal animals, an increase in the duration of the period of inhibition to repeated stimulation could not be demonstrated. In this preparation, a gradual decrease in inhibition occurred. It is tentatively concluded that inhibition of spinal interneurones, the development of which depends upon descending influences from supraspinal centres, may be partially responsible for habituation.     

Effects of systemic administration of strychnine, L-allylglycine, bicuculline and picrotoxin on the transsynaptic neural destruction in the medullary dorsal horn following transection of the rat inferior alveolar nerve

Adult rats underwent unilateral transection of the inferior alveolar nerve and subsequent intraperitoneal injection of strychnine (1 mg/kg, 3-23 days) at various posttransectional intervals. When they were sacrificed at 18-30 days posttransectionally, many pyknotic neuronal cell bodies were observed in plastic embedded toluidine blue-stained 1 micron-thick sections of the medullary dorsal horn. They were mostly found in the dorsal part of the dorsal horn ipsilateral to the neurotomy and were more abundant in laminae I/II than in laminae III/IV. Similar pyknotic neurons were found after 1 or 2 days of L-allylglycine administration (55.7 mg/kg/day) at a posttransectional interval of 20 days. Unlike those observed after strychnine treatment, the pyknotic neurons after L-allylglycine treatment were evenly distributed throughout laminae I-IV of the dorsal half of the medullary dorsal horn. Twenty-three days of bicuculline (2 mg/kg/day) or picrotoxin (0.5 mg/kg/day) treatment at an interval of 7 days did not yield pyknotic neurons. The results are discussed in the light of intrinsic synaptic circuitry of the dorsal horn.     

The effect of strychnine, bicuculline, and picrotoxin on X and Y cells in the cat retina

The effect of intravenous strychnine and the GABA antagonists picrotoxin and bicuculline upon the discharge pattern of center-surround-organized cat retinal ganglion cells of X and Y type were studied. Stimuli (mostly scotopic, and some photopic) were selected such that responses from both on and off-center cells were either due to the center, due to the surround, or clearly mixed. Pre-drug control responses were obtained, and their behavior following administration of the antagonists was observed for periods up to several hours. X-cell responses were affected in a consistent manner by strychnine while being unaffected by GABA antagonists. All observed changes following strychnine were consistent with a shift in center-surround balance of X cells in favor of the center. For Y-cell responses to flashing annuli following strychnine, there was either no shift or a relatively small shift in center-surround balance. Compared to X-cell responses to flashing lights, those of Y cells were very little affected by strychnine and in most cases were unaffected. It thus appears that glycine plays a similar role in receptive field organization of X cells as does GABA in Y cells (Kirby and Enroth-Cugell, 1976. J. Gen. Physiol. 68:465-484).     

Effects of anticonvulsant agents and ethanol on the complexes of epileptic foci created by applications of bicuculline, strychnine, and penicillin in the rat brain cortex

Anticonvulsive effects of direct agonists of the GABA receptor system, medinal and phenazepam, as well as ethanol, on the complexes of epileptic foci created in the rat brain cortex by applications of various convulsant agents (bicuculline, strychnine, or penicillin) were studied. Ethanol, as well as phenazepam and medinal, were shown to possess high anti-epileptic activity in relation to the complexes. It was shown, using an i.v. infusion technique, that threshold doses of strychnine and bicuculline depend, in a linear and a nonlinear fashion, respectively, on the alcohol doses administered. A specific feature was found in the pharmacolgoical effect of ethanol: anticonvulsive activity of ethanol was pronounced within the postinjection interval from 5 min to 4 h, while within the following interval, from 4 to 24 h, the animals turned into a seizure-ready state. The subseizure phase was observed under the conditions when the penicillin complex was induced, and also following i.v. injections of strychnine and bicuculline.     

Transfer of habituation in Aplysia: contribution of heterosynaptic pathways in habituation of the gill-withdrawal reflex

Habituation of the Aplysia gill-withdrawal reflex (and siphon-withdrawal reflex) has been attributed to low-frequency homosynaptic depression at central sensory-motor synapses. The recent demonstration that transfer of habituation between stimulation sites occurs in this model system has prompted the hypothesis that heterosynaptic inhibitory pathways also play a role in the mediation of habituation behavior. To test this hypothesis, the sites and mechanisms of neural plasticity which underlie transfer of habituation in Aplysia were examined. Transfer of habituation is a reduction in the reflex evoked at one stimulation site (siphon) due to repeated presentation of a stimulus to a second site (gill). Centrally mediated transfer of habituation, measured in a preparation lacking the siphon-gill peripheral nervous system (PNS), was associated with a reduced excitatory response in central motor neurons. Repeated tactile stimulation of the gill did not attenuate the gill response evoked by electrical stimulation of the branchial nerve nor the mechanoreceptor response recorded in LE sensory neurons. In contrast, repeated stimulation of siphon or gill at a site which was "off" the sensory field of a specific mechanoreceptor led to a diminution in synaptic transmission between that sensory neuron and its followers (motor neurons and inter-neurons). These data demonstrate that centrally mediated transfer of habituation results from heterosynaptic modulation of synaptic transmission at the sensory-motor (and sensory-interneuron) synapses. Therefore, habituation behavior in Aplysia is mediated through the conjoint action of homosynaptic and heterosynaptic inhibitory processes.     

Effects of spinal transection on presynaptic markers for glutamatergic neurons in the rat

To evaluate the hypothesis that glutamic acid may be the neurotransmitter of descending, excitatory supraspinal pathways, the uptake and release ofl-[³H] glutamate and the levels of endogenous glutamate were measured in preparations from rat lumbar spinal cord following complete mid-thoracic transection. Following transection, the activity of the synaptosomal high-affinty glutamate uptake process was increased in both dorsal and ventral halves of lumbar cord between 1 and 14 days after transection and returned to control levels by 21 days posttransection. At 7 days, the increased activity of the uptake process forl-[³H] glutamate resulted in elevation ofV _max with no significant alteration inK _t as compared to age-matched controls. Depolarization-induced release ofl-[³H]glutamate from prelabeled slices did not differ significantly from control in the lesioned rat except at 21 days after lesion when the amount of tritium release was significantly greater in the transected preparations than in control. Amino acid analysis of the lumbar cord from control and transected rats indicated only a 10% decrease in the level of endogenous glutamate and no alterations in the concentration of GABA and glycine 7 days after lesion. These findings do not support the hypothesis that glutamate serves as a major excitatory neurotransmitter in supraspinal pathways innervating the lumbar cord of the rat.