Practical methods for the synthesis of (R)or (S)-2,2'-bis(diarylphosphino)-l,l'-binaphthyls (BINAPs), useful ligands for transition-metal-catalyzed asymmetric reactions, have been developed. (±)-2,2'-Bis(diphenylphosphinyl)-l,l'-binaphthyl [(±)-BINAPO], prepared from 2,2'-dibromo-l,l'-binaphthyl and diphenylphosphinyl chloride, can be resolved into optical antipodes by the use of camphorsulfonic acid or 2,3-di-O-benzoyltartaric acid. Reduction of resolved BINAPO with trichlorosilane in the presence of triethylamine affords optically pure 2,2'-bis(diphenylphosphino)-l,l'-binaphthyl (BINAP). In a similar manner, several BINAP analogues have been prepared in optically pure form. The present procedures are suitable for obtaining these axially dissymmetric diphosphines in a large scale. The molecular structure of the 1:1:1 complex of (S)-(-)-BINAPO, (lR)-(-)-camphorsulfonic acid, and acetic acid has been studied by single-crystal X-ray analysis.Recently numerous chiral di-terf-phosphines have been devised as ligands for transition-metal-catalyzed asym-metric syntheses in the homogeneous phase.1 Some years ago, we reported (R)or (S)-2,2'-bis(diphenyl-

Synaptic inputs to nucleus laminaris (NL) neurones were studied in a brainstem slice preparation of chick embryos (E15‐20) using the whole‐cell patch clamp technique. NL neurones are third order auditory neurones and are proposed to behave as coincidence detectors concerned with interaural timing discrimination. Under voltage clamp conditions, electrical stimuli applied to either ventral or dorsal dendritic layers evoked EPSCs. These fast currents decayed with a time constant of 1.1 ms near the resting potential, reversed close to 0 mV, and were blocked by 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX, 20 μM) or 6,7‐dinitro‐quinoxaline‐2,3‐dione (DNQX, 20 μM). Coincident or near coincident stimulation of the ventral and the dorsal dendritic layers increased the probability of action potential generation (response probability). In the presence of CNQX (40 μM) other postsynaptic currents (PSCs) were observed, which reversed close to the equilibrium potential for chloride (ECl), and were reversibly blocked by bicuculline (20 μM) and, therefore, were mediated by GABAA receptors. Spontaneous GABAergic PSCs were inward going near the resting membrane potential immediately after starting whole‐cell recording with a low Cl− (5 mM, ECl= ‐90 mV) pipette medium, but became outward‐going with time. This indicates that GABAergic inputs may generate depolarizing potentials in intact NL neurones. Local GABA (10 μM) application reduced both the EPSP and EPSC amplitude and shortened the EPSP decay time constant (from 5.3 to 2.1 ms), while the EPSC decay time constant was not affected (from 1.3 to 1.2 ms). These GABA effects were mostly due to the shunting conductance of the postsynaptic GABAA receptors. Depolarizing current injections combined with electrical stimuli to a unilateral axon bundle simulated bilateral synaptic inputs. Response probability increased with decreased interstimulus intervals, while local GABA (10 μM) application to the soma narrowed the time dependence of the response probability. These results suggest that GABAergic inputs to NL neurones may serve to improve coincidence detection of the bilateral excitatory inputs through an increase in membrane conductance.

Correlated spontaneous activity in the resting brain is increasingly recognized as a useful index for inferring underlying functional-anatomic architecture. However, despite efforts for comparison with anatomical connectivity, neuronal origin of intrinsic functional connectivity (inFC) remains unclear. Conceptually, the source of inFC could be decomposed into causal components that reflect the efficacy of synaptic interactions and other components mediated by collective network dynamics (e.g., synchronization). To dissociate these components, it is useful to introduce another connectivity measure such as effective connectivity, which is a quantitative measure of causal interactions. Here, we present a direct comparison of inFC against emEC (effective connectivity probed with electrical microstimulation [EM]) in the somatosensory system of macaque monkeys. Simultaneous EM and functional magnetic resonance imaging revealed strong emEC in several brain regions in a manner consistent with the anatomy of somatosensory system. Direct comparison of inFC and emEC revealed colocalization and overall positive correlation within the stimulated hemisphere. Interestingly, we found characteristic differences between inFC and emEC in their interhemispheric patterns. Our results suggest that intrahemispheric inFC reflects the efficacy of causal interactions, whereas interhemispheric inFC may arise from interactions akin to network-level synchronization that is not captured by emEC.

Neurons in the nucleus laminaris detect the coincidence of binaural signals, and are the first neurons to calculate the interaural time difference for the sound source localization in birds. In this paper, we have studied contributions of synaptic depression to the coincidence detection in the nucleus laminaris in a slice preparation of the chick embryo (E16-18), using the whole-cell patch recording technique. Under voltage clamp, EPSCs decreased progressively in their amplitude during the course of tetanic stimuli. This synaptic depression was primarily ascribed to the reduction of transmitter release from the presynaptic terminal, because the depression was decreased by reducing transmitter release with 2.5 microm Cd2+ but was not affected by reducing desensitization of postsynaptic AMPA receptors with 20 microm cyclothiazide. Under current clamp, trains of 10 stimuli of 100 Hz were applied bilaterally with changing the time intervals systematically between both sides. Response window, defined as the time interval corresponding to the half-maximum firing probability, was narrowed during the course of the stimulus train, and this occurred in parallel with a decrease in the EPSP amplitude. In addition, the reduction of the EPSP amplitude due to 2.5 microm Cd2+ or 2 microm CNQX improved the accuracy of coincidence detection. These results indicate that the synaptic depression may improve the coincidence detection in the chick laminaris neurons.

Utilizing slice preparations of GAD67-GFP knock-in mouse, in which GABAergic neurons are specifically labeled with GFP fluorescence, we studied electrophysiological characteristics of GABAergic neurons of IC by whole-cell patch clamp-recording combined with biocytin-intracellular-staining techniques. GABAergic neurons of IC fell into two distinct firing types; (1) tonic type neurons and (2) transient (phasic) type neurons. Tonic type neurons showed regularly repetitive discharge pattern in response to a long depolarizing current pulse (200 ms), and transient type neurons showed spike discharges just at the onset of current pulse. Most of neurons of both types showed depolarizing sag in response to hyperpolarizing current pulse, which were blocked by 0.1 mM ZD7288 (Ih blocker). All two types of tonic neurons showed an AHP, which was blocked by Cd2+ (0.1 mM) and high concentration of apamin (2 microM). One of tonic type neurons (BP) revealed a long delay in spike onset or a longer first spike interval when they were stimulated from hyperpolarized potentials. The remaining tonic neurons (RS) did not show this property. Tonic type neurons were distributed in all region of IC. Morphologically, they were not identical; heterogeneous in somatic diameter, dendritic field size and its orientation. One of transient type neurons (Th-) revealed an AHP after the spike. The other transient type neurons (Th+) showed a depolarization hump after the spike, which were blocked by 0.1-0.2 mM Ni2+. Th+ type neurons were found only in the dorsolateral region of IC, having small dendritic field. Th+ type neurons are likely to be a distinct, homogenous group of GABAergic neuron in IC.