Diminution of Voltage Threshold Plays a Key Role in Determining Recruitment of Oculomotor Nucleus Motoneurons during Postnatal Development

The size principle dictates the orderly recruitment of motoneurons (Mns). This principle assumes that Mns of different sizes have a similar voltage threshold, cell size being the crucial property in determining neuronal recruitment. Thus, smaller neurons have higher membrane resistance and require a lower depolarizing current to reach spike threshold. However, the cell size contribution to recruitment in Mns during postnatal development remains unknown. To investigate this subject, rat oculomotor nucleus Mns were intracellularly labeled and their electrophysiological properties recorded in a brain slice preparation. Mns were divided into 2 age groups: neonatal (1–7 postnatal days, n = 14) and adult (20–30 postnatal days, n = 10). The increase in size of Mns led to a decrease in input resistance with a strong linear relationship in both age groups. A well-fitted inverse correlation was also found between input resistance and rheobase in both age groups. However, input resistance versus rheobase did not correlate when data from neonatal and adult Mns were combined in a single group. This lack of correlation is due to the fact that decrease in input resistance of developing Mns did not lead to an increase in rheobase. Indeed, a diminution in rheobase was found, and it was accompanied by an unexpected decrease in voltage threshold. Additionally, the decrease in rheobase co-varied with decrease in voltage threshold in developing Mns. These data support that the size principle governs the recruitment order in neonatal Mns and is maintained in adult Mns of the oculomotor nucleus; but during postnatal development the crucial property in determining recruitment order in these Mns was not the modifications of cell size-input resistance but of voltage threshold

The effect of two lipophilic gamma-aminobutyric acid uptake blockers in CA1 of the rat hippocampal slice

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 gamma-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 CA1 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

Post-reinforcement pauses and response rate of monkeys on a two-hand fixed-ratio schedule

Fixed-ratio behavior of monkeys was analyzed separately for two hands. While one hand responded on the fixed-ratio schedule the other performed a holding response and the function of the hands changed in alternate ratio runs. After performance was stable on the fixed ratio (70 responses, two monkeys; 100 responses, two monkeys, 120 responses, two monkeys) 90 sessions of further training equalized post-reinforcement pauses and the mean interresponse time of the two hands. Hand preference in reaching for food remained unchanged. Then, the fixed-ratio requirement was changed (a) in small sequential steps, (b) in two large steps, and, (c) within sessions alternating two runs at a high ratio with two runs at a low ratio. The mean duration of post-reinforcement pauses was correlated with a fixed ratio maintained throughout a session but single pauses were neither controlled by the immediately preceding nor by the following ratio run when a cue to its length was available. The mean interresponse time was insensitive to changes in fixed ratio. The fixed-ratio performance was generally similar to that of pigeons and rats