Most in vitro studies of D 1 dopaminergic modulation of excitability in neostriatal medium spiny neurons have revealed inhibitory effects. Yet studies made in more intact preparations have shown that D 1 receptors can enhance or inhibit the responses to excitatory stimuli. One explanation for these differences is that the effects of D 1 receptors on excitability are dependent on changes in the membrane potential occurring in response to cortical inputs that are seen only in intact preparations. To test this hypothesis, we obtained voltage recordings from medium spiny neurons in slices and examined the impact of D 1 receptor stimulation at depolarized and hyperpolarized membrane potentials. As previously reported, evoked discharge was inhibited by D 1 agonists when holding at negative membrane potentials (approximately Ϫ80 mV ). However, at more depolarized potentials (approximately Ϫ55 mV ), D 1 agonists enhanced evoked activity. At these potentials, D 1 agonists or cAMP analogs prolonged or induced slow subthreshold depolarizations and increased the duration of barium-or TEAinduced Ca 2ϩ -dependent action potentials. Both effects were blocked by L-type Ca 2ϩ channel antagonists (nicardipine, calciseptine) and were occluded by the L-type channel agonist BayK 8644 -arguing that the D 1 receptor-mediated effects on evoked activity at depolarized membrane potential were mediated by enhancement of L-type Ca 2ϩ currents. These results reconcile previous in vitro and in vivo studies by showing that D 1 dopamine receptor activation can either inhibit or enhance evoked activity, depending on the level of membrane depolarization.

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It is demonstrated that acetylcholine released from cholinergic interneurons modulates the excitability of neostriatal projection neurons. Physostigmine and neostigmine increase input resistance (RN) and enhance evoked discharge of spiny projection neurons in a manner similar to muscarine. Muscarinic RN increase occurs in the whole subthreshold voltage range (-100 to -45 mV), remains in the presence of TTX and Cd2+, and can be blocked by the relatively selective M1,4 muscarinic receptor antagonist pirenzepine but not by M2 or M3 selective antagonists. Cs+ occludes muscarinic effects at potentials more negative than -80 mV. A Na+ reduction in the bath occludes muscarinic effects at potentials more positive than -70 mV. Thus, muscarinic effects involve different ionic conductances: inward rectifying and cationic. The relatively selective M2 receptor antagonist AF-DX 116 does not block muscarinic effects on the projection neuron but, surprisingly, has the ability to mimic agonistic actions increasing RN and firing. Both effects are blocked by pirenzepine. HPLC measurements of acetylcholine demonstrate that AF-DX 116 but not pirenzepine greatly increases endogenous acetylcholine release in brain slices. Therefore, the effects of the M2 antagonist on the projection neurons were attributable to autoreceptor block on cholinergic interneurons. These experiments show distinct opposite functions of muscarinic M1- and M2-type receptors in neostriatal output, i.e., the firing of projection neurons. The results suggest that the use of more selective antimuscarinics may be more profitable for the treatment of motor deficits.

EEG spectral parameters were computed in a group of children with different degrees of difficulty in learning to read and write. For statistical analyses, Z-transformed values according to normative age-regression equations were used to control the age effects. Canonical Correlation Analysis between absolute power in different bands and the categories of the educational evaluation (good, regular, poor and very poor) showed that more delta was probably related to a poor evaluation and more alpha in occipital areas to a good one. MONOVA also showed highly significant differences in the absolute power in many leads between children with different evaluations. As children with a poor evaluation very frequently had antecedents of risk factors related to brain damage and were from a low socioeconomic status, and both factors have been shown to affect absolute power, it may be that the differences observed were due to these causes. However, relative power correlated more with the learning problems. Children with minor difficulties, with no antecedents and with good socioeconomic status had more theta in almost all leads than children with a good evaluation and with the same characteristics. Children with a poor, or very poor, evaluation had more delta in left frontal and temporal areas (F3, F7 and T3) which may reflect underlying cerebral dysfunction of these regions directly involved in reading and writing processes.