Faculty Bibliography

This article reviews the electroresponsive properties of single neurons in the mammalian central nervous system (CNS). In some of these cells the ionic conductances responsible for their excitability also endow them with autorhythmic electrical oscillatory properties. Chemical or electrical synaptic contacts between these neurons often result in network oscillations. In such networks, autorhythmic neurons may act as true oscillators (as pacemakers) or as resonators (responding preferentially to certain firing frequencies). Oscillations and resonance in the CNS are proposed to have diverse functional roles, such as (i) determining global functional states (for example, sleep-wakefulness or attention), (ii) timing in motor coordination, and (iii) specifying connectivity during development. Also, oscillation, especially in the thalamo-cortical circuits, may be related to certain neurological and psychiatric disorders. This review proposes that the autorhythmic electrical properties of central neurons and their connectivity form the basis for an intrinsic functional coordinate system that provides internal context to sensory input

Microfluorometric imaging was used to study the correlation of intracellular calcium concentration with voltage-dependent electrical activity in guinea pig cerebellar Purkinje cells. The spatiotemporal dynamics of intracellular calcium concentration are demonstrated during spontaneous and evoked activity. The results are in agreement with hypotheses of dendritic segregation of calcium conductances suggested by electrophysiological experiments. These in vitro slice fluorescence imaging methods are applicable to a wide range of problems in central nervous system biochemical and electrophysiological functions

The performance of a cryogenic system that monitors the extracranial magnetic field simultaneously at 14 positions over the scalp has been evaluated to determine the accuracy with which neuronal activity can be located within the human brain. Initially, measurements were implemented on two model systems, a lucite sphere filled with saline and a model skull. With a magnetic field strength similar to that of a human brain, the measurement and analysis procedures demonstrated a position accuracy better than 3 mm, for a current dipole 3 cm beneath the surface. Subsequently, measurements of the magnetic field pattern appearing 100 ms after the onset of an auditory tone-burst stimulus were obtained in three human subjects. The location of the current dipole representing intracellular ionic current in active neurons of the brain was determined, with 3-mm accuracy, to be within the cortex forming the floor of the Sylvian fissure of the individual subjects, corresponding closely to the Heschl gyrus as determined from magnetic resonance images. With the sensors placed at appropriate positions, the locations of neuronal sources for different tone frequencies could be obtained without moving the recording instrument. Adaptation of activity in human auditory cortex was shown to reveal long-term features with a paradigm that compared response amplitudes for three tones randomly presented

1. We describe here a technique which allows the long-term in vitro survival of the perfused isolated brain stem-cerebellum of adult guinea-pig. The viability of this preparation was assessed by comparing the electrophysiological properties of individual neurones and of neuronal pools to those obtained in vivo or in brain slices. The areas investigated included the cerebellar cortex, the inferior olive and the pontine nuclei. 2. Cerebellar field potential and intra- and extracellular single-cell recordings could be obtained for as long as 15 h after the preparation was initially isolated. The waveforms of field potentials recorded at various depths in the cerebellar cortex following surface folial stimulation were similar to those recorded in vivo. Extracellular recordings from single Purkinje cells following white matter stimulation demonstrated antidromic as well as mossy- and climbing fibre-mediated excitation. Stimulation of the cerebellar surface elicited orthodromic parallel fibre excitation of Purkinje cells and basket-stellate and Golgi cell inhibition. 3. Intrasomatic and intradendritic recordings from Purkinje cells reproduced all the phenomenology described earlier under in vivo conditions and in vitro slice preparations. In addition, spontaneous excitatory synaptic potentials generating simple spikes (mossy fibre-parallel fibre-mediated activity) and complex spikes (climbing fibre-mediated activity) were consistently observed. 4. Extracellular field potentials and extra- and intracellular recordings from inferior olive neurones were similar to those previously shown for the mammalian inferior olive. 5. Intracellular recordings were also obtained from pontine nuclei neurones, a major source of mossy fibre afferents to the cerebellum. Stimulation of the contralateral superior cerebellar peduncle produced antidromic invasion of these neurones whereas stimulation of the ipsilateral inferior cerebral peduncle resulted in their orthodromic activation. 6. The preparation responded to pharmacological challenge in a manner which demonstrated a sequential activation of sets of synaptic links in a given pathway. Thus, harmaline generated oscillations of inferior olivary neurones which were similar to those observed in vivo and which produced climbing fibre EPSPs in Purkinje cells at the same frequency as the inferior olivary oscillations. Climbing fibre activation of the Purkinje cells generated powerful inhibitory potentials in the cerebellar nuclear neurones at the same frequency.(ABSTRACT TRUNCATED AT 400 WORDS)

1. Intracellular recordings were obtained from cerebellar nuclear neurones in the isolated brain stem-cerebellar preparation of guinea-pigs in vitro. The electrical properties of the cells were quite similar to those reported in in vitro slice studies. They had an average resting potential of -56.7 +/- 1.8 mV, an input resistance of 23.8 +/- 4.9 M omega, and a time constant of 12.5 +/- 2.7 ms. The action potentials had an average amplitude of 57.3 +/- 5.28 mV (n = 20). 2. In addition to the ionic mechanisms required for the generation of the fast action potential, cerebellar nuclear neurones displayed a low-threshold Ca2+-dependent spike which produced a powerful rebound excitation following anodal break. This type of electroresponsiveness was absent in the slice preparation. 3. The anodal break response was further enhanced by the presence of a non-inactivating Na+ conductance similar to that described in Purkinje cells. 4. Following electrical stimulation of the cerebellar cortex or the underlying white matter, excitatory and inhibitory synaptic potentials (EPSP-IPSP sequences) could be recorded in cerebellar nuclear neurones. The EPSPs were elicited by direct activation of collaterals of mossy or climbing fibre afferents. The IPSPs followed direct or orthodromic Purkinje cell activation. 5. The integrity of the olivo-cerebellar system was tested by the administration of harmaline which produced powerful EPSP-IPSP sequences or pure IPSPs in cerebellar nuclear neurones. These IPSPs were often followed by a rebound firing of the cells. 6. These results indicate that the olivo-cerebellar pathway, in addition to its activation of the cerebellar cortex, exerts a powerful and complex set of synaptic events on cerebellar nuclear cells. As such it is a true afferent system, having a distinct role in cerebellar physiology