1. Extra-and intracellular recordings were made from CA1 cells in hippocampal slices in vitro. The effects of ionophoretically applied GABA on somatic and dendritic regions were studied. 2. Jonophoresis of GABA at dendritic sites gave a reciprocal effect by inhibiting the effect of excitatory synapses close to the dendritic application, while facilitating those lying further away. For example, GABA delivered to the mid-radiatum dendritic region reduced the population spike generated by a radiatum volley, while facilitating the population spike evoked by oriens fibre stimulation. Similarly, when single cells were recorded from, mid-apical dendritic delivery of GABA abolished the synaptically driven discharges evoked by fibres terminating at this part of the dendritic tree, but facilitated the responses to input from fibres terminating on the basal dendrites of the same cell. 3. With intracellular recording two effects were observed. Applied near the soma, GABA induced a hyperpolarization associated with an increased membrane con-ductance. When applied to dendrites, GABA caused a depolarization also associated with an increased membrane conductance. Both types of GABA applications could inhibit cell discharges, although in some cases the depolarizing response could facilitate other excitatory influences or cause cell firing by itself. 4. Both the hyperpolarizing and depolarizing GABA responses persisted after blockade of synaptic transmission by applying a low calcium high magnesium solution, indicating mediation via a direct effect upon the cell membrane. 5. The reversal potential for the hyperpolarizing GABA effect was similar to the equilibrium potential for the i.p.s.p. evoked from alveus or orthodromically, and was 10-12 mV more negative than the resting potential. The size of the depolarizing response was also dependent upon the membrane potential. By extrapolation an estimated equilibrium potential was calculated as about-40 mV. 6. Our results support the idea that the hyperpolarizing basket cell inhibition at the soma is mediated by the release of GABA. This hyperpolarizing response causes a general inhibition of firing. The dendritic effects of GABA, however, seem to repre-* Present address:

SUMMARY1. We trained monkeys to jump down from different heights, and recorded electromyograms (e.m.g.s) in arm muscles, and ground reaction forces. The landing movements were also recorded by high-speed cinematography.2. The e.m.g. of the triceps began about 80 ms before landing. The initial burst lasted until about 20 ms after ground contact and was succeeded by bursts of gradually declining amplitude. These discharges were not of reflex origin, because when the monkey was deceived by a collapsible platform, they were time-locked to the expected, not to the true landing.3. The amplitude of the e.m.g. in the triceps increased with the height of the jump, indicating adaptive control.4. The timing of the e.m.g. pattern was assumed to be programmed before take off, because it was unaffected by extinction of the light during the fall.5. The vertical ground reaction force produced by the arms had an inflexion on its rising phase which arose from the very rapid stretch of the muscles which control the wrist. Then came a sharp peak produced mainly by stretch of the triceps. The inflexion and the sharp peak were probably produced by short-range stiffness of the muscles of the upper arm.6. The torque acting on the elbow joint, and the elbow joint stiffness were calculated from the ground reaction forces and the movement of the arm. The torque was high at impact and gradually declined during the landing. The force produced by the triceps increased sharply, then decreased while it continued to lengthen. Thus, the elbow joint showed high initial stiffness, which then decreased, and finally became negative. This dynamic relation between length and tension was very different from the static length-tension characteristic of skeletal muscles. The observed behaviour of the muscles presumably takes advantage of the resistance of the musculo-skeletal system to transient forces.7. The observed negative stiffness occurs only during submaximal contractions. We propose that the segmented pattern in the e.m.g. produces submaximal contractions in both slow and fast fibres in spite of a high excitatory drive.

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1 Drugs that increase inhibitory synaptic transmission in the central nervous system may be valuable tools in the treatment of seizures. Theoretically, substances that block the uptake of inhibitory transmitters such as y-aminobutyric acid (GABA) into intracellular compartments should also increase inhibition and therefore have potential value as antiepileptic drugs. However, most of these substances penetrate the blood-brain barrier poorly and have therefore until now had limited value. NO-05-0328 and NO-05-0329 are two new lipophilic GABA uptake inhibitors that readily enter the CNS from the blood. 2 We have investigated the effect of these two uptake inhibitors on the responses to exogenous GABA and on GABA-mediated inhibitory synaptic potentials in pyramidal neurones of the CAI region in the rat hippocampal slice. 3 We found that both drugs increased the amplitude and duration of responses to exogenous GABA. Furthermore, the inhibitory synaptic potentials increased in amplitude. This increase was seen in both early and late phases of the synaptic potentials. We conclude that NO-05-0328 and NO-05-0329, at least in vitro, are more effective than older GABA uptake inhibitors such as nipecotic acid and they therefore deserve consideration for clinical use.

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