John C. Eccles

Afferent volleys in limb nerves influencing impulse discharges in cerebellar cortex II. In purkyně cells

SummaryImpulses discharged by Purkyně cells provide the only output from the cerebellar cortex. Usually the Purkyně cells can be identified with certainty because they alone respond by the brief bursting discharge generated by climbing fiber (CF) impulses, as well as by the ubiquitous simple spikes. The discharges from single Purkyně cells in the anterior lobe have been studied in lightly anesthetized and in decerebrate unanesthetized cats. All of our 275 identified cells had an average background discharge frequency in the range of 5/sec to 100/sec. The discharge was increased and/or depressed by afferent volleys from a number of limb nerves. In addition there was usually a slow rate of CF-evoked spike bursts at 0.5–2/sec, and many afferent inputs also evoked CF responses.The firing patterns of Purkyně cells are often very irregular, but by the technique of computer averaging of many sweeps, usually 128, the responses of the cell under observation have been accurately and reliably displayed as post-stimulus time histograms and their cumulative frequency distributions. In this manner the distinctive features of the responses evoked by the mossy fiber and climbing fiber inputs have been determined under a wide variety of conditions. The most direct mossy fiber responses — excitatory or inhibitory — had a shorter latency than the climbing fiber responses, usually by more than 10 msec. However, there were also later responses to both types of input.Repetitive afferent volleys were used to study facilitation of the mossy fiber responses at short intervals, and the effectiveness of repetition on both kinds of inputs at slower frequencies. Repetitive mossy fiber inputs apparently can give a maintained enhancement or depression of the Purkyně cell discharge.

Cutaneous mechanoreceptors influencing impulse discharges in cerebellar cortex. II. In Purkyně cells by mossy fiber input

SummaryThis paper gives an account of single Purkyně cell responses when three types of mechanical stimulation, as in the previous paper, are applied to the forefoot and hindfoot of the decerebrate unanesthetized cat. Attention was concentrated on the effects of brief mechanical pulses to the footpad. Recording was extracellular by glass microelectrodes and special precautions were taken in identifying the spike responses as being due to a single Purkyně cell and in securing its effective isolation for our computer averaging techniques, as described in the previous papers. All Purkyně cells were in the ipsilateral anterior lobe in the lateral vermis or pars intermedia of lobules III, IV, V, except for a few recordings in the extreme rostral zone of lobule VI.Mechanical pulses or taps evoked responses from many Purkyně cells which were pure excitatory, pure inhibitory or admixtures thereof. The latencies of onset were usually in the range of 12–20 msec from the onset of the tap, which tends to be a little longer than the observed latencies for mossy fiber responses described in the preceding paper. There was often a considerable difference in the sizes of the responses evoked from different pads of the same foot, and the usual threshold for response was below 0.2 mm amplitude. Durations of responses were usually 10–20 msec for excitation and 50–100 msec for inhibition.Pressure pulses to the central foot pads of 2 sec duration evoked a wide variety of responses: brief phasic at “on” and “off” that could be admixtures of excitation and inhibition; almost pure tonic excitations or inhibitions that were well maintained during the 2 sec; phasic-tonic responses in various relative degrees. Usually 500 g was maximally effective and the threshold was below 100 g.Hair receptors were stimulated preferentially by brief air jets, there being brief excitatory or inhibitory responses much as with taps, but with rather longer latency. The effective area was usually fairly extensive over the hairy skin of the foot.In general the effects on Purkyně cells by cutaneous mechanoreceptors acting via mossy fibers were in accord with the mossy fiber responses reported in the preceding paper and with the well-known excitatory and inhibitory effects that are exerted by mossy fiber inputs on Purkyně cells.

Integration by Purkyně cells of mossy and climbing fiber inputs from cutaneous mechanoreceptors

SummaryThe preceding two papers gave accounts of mossy fiber (MF) or of climbing fiber (CF) inputs to Purkyně cells under conditions where the other input was depressed by the experimental procedure. By utilizing either chloralose anesthesia or decerebration with sparing of the pyramidal tracts it has been possible to study the convergence of MF and CF inputs onto single Purkyně cells. The stimulation of cutaneous mechanoreceptors, the recording procedures for unitary Purkyně cell discharges and the computer averaging techniques were as previously described.Testing by taps to the footpads evoked a combined MF and CF response more commonly than either response alone, and often both inputs were very effective. There was a tendency for such phasic CF responses to be more frequently observed than the tonic responses to pad pressure, but such responses did occur.Purkyně cells were located by the usual procedure along the microelectrode tracks later identified in serial sections. Those cells activated by the fast MF inputs from the pad receptors were found to be closely associated in groups or colonies. The delayed MF inputs probably via spino-reticular pathways were more widely dispersed. The topographical relationships of these colonies are displayed on maps of the unfolded cerebellar cortex for lobules II to VI of both vermis and pars intermedia. In general these distributions of Purkyně cells activated from forefoot and hindfoot appear as islands in the larger fields that degeneration procedures exhibit for the cuneocerebellar and dorsal spinocerebellar tracts respectively. The CF inputs from the footpads also project to these same colonies, so that there are conjoint MF and CF colonies.The several modalities of the cutaneous mechanoreceptors of the forefoot or hindfoot often participate in the receptive fields of individual Purkyně cells. Such a field may be restricted to one or other side of the foot, all tested cutaneous mechanoreceptors then sharing approximately in the same restriction. Finally it is shown how these experimental findings relate to the theories of cerebellar function, particularly to the dynamic loop hypothesis.

Investigations on integration of mossy fiber inputs to Purkyně cells in the anterior lobe

SummaryThe 275 Purkyně cells identified by the criteria of the previous paper have been investigated with respect to their role as units integrating the input to the anterior lobe from various limb nerves. The discharges from single Purkyně cells have been studied in lightly anesthetized (pentothal) or in decerebrate unanesthetized cats, there being averaging usually of 128 responses in the form of post-stimulus time histograms and cumulative frequency distributions.Single Purkyně cells exhibited a wide variation in their responses to the diverse inputs from the various afferent nerves. Attention was focussed on excitatory and inhibitory responses evoked by mossy fibers with a short latency, usually 10–15 msec for hindlimb afferents. With most Purkyně cells these responses were predominantly evoked from cutaneous nerves, low threshold fibers being particularly effective. A few Purkyně cells were preponderantly excited by afferent volleys from muscle nerves, but there was a large group with a mixed input from cutaneous and muscle nerves. Graded strengths of stimulation of muscle nerves showed that sometimes group I volleys were prepotent, but other Purkyně cells were selectively excited by group II volleys. Though sometimes the afferent volleys from antagonistic muscles had a reciprocal action on a Purkyně cell, as on a motoneurone, it was more common to find similar actions. Also convergence of inputs from forelimb and hindlirnb nerves, both cutaneous and muscular, was not uncommon, particularly in marginal areas between hindlimb and forelimb zones. A special design feature is the convergence onto a Purkyně cell of mossy fiber and climbing fiber inputs evoked by the same afferent volley. This convergence was of particular interest along the parasagittal strip of hindlimb climbing fiber distribution in lobule V.It was not possible to translate the observations into some map of the cerebellar cortex on which are marked the territorial distributions from the various limb afferent nerves. Rather, there was an ill-defined patchy character, closely adjacent Purkyně cells often receiving very different subsets of the total input from the various limb nerves. The unitary integrations accomplished by the individual Purkyně cells are further integrated when their axons converge onto and inhibit the neurones of the cerebellar nuclei, and this integration by convergence would occur in each successive relay on the output pathways from the cerebellum.It is pointed out that the experimental findings on the integrative action of the individual Purkyně cells provide basic information for attempts to construct models simulating cerebellar performance and control.

Brain, speech and consciousness

The language centres are restricted to the dominant cerebral hemisphere and are associated with special hypertrophied zones. In a number of subjects the enormous commissure linking the two cerebral hemispheres has been completely severed for therapeutic reasons, and Sperry has investigated the associated disabilities. The outstanding discovery is the uniqueness and exclusiveness of the dominant hemi-. sphere in respect of conscious experience. The minor hemisphere exhibits a refined performance in respect of pattern and form but gives no conscious experience to the subject. The hypothesis is developed that normally the neural events in the minor hemisphere do not directly give the subject any conscious experiences. There is finally a discussion of the primacy of consciousness in respect of cerebral function, both in receiving and giving to the neuronal mechanisms of the liaison area of the dominant hemisphere. A reference is made to the immense and fundamental problems that are involved in brain evolution as primitive man developed means of communication in speech.

Cutaneous mechanoreceptors influencing impulse discharges in cerebellar cortex. I. In mossy fibers

SummaryThis paper gives an account of single mossy fiber responses when three types of mechanical stimulation are applied to the forefoot and hindfoot of the cat which is either decerebrate and unanesthetized or lightly anesthetized by pentothal or chloralose. The mechanical stimuli were applied either to footpads (brief pulses, taps, or longer square pulses or ramps) or to the hairy skin by air jets.Recording of single mossy fibers was extracellular by glass microelectrodes that were inserted into the granular layer of the cerebellar cortex or the subjacent white matter. As described in previous papers computer averaging techniques usually of 64 responses have been employed to enhance reliability.Taps evoked pure excitatory responses from many mossy fibers, which were usually brief high frequency bursts resembling those evoked by nerve volleys. Usually the threshold displacement was less than 0.2 mm and thresholds as low as 0.01 mm were observed. There were often considerable differences in the intensities of responses from different pads of the same foot. Successive pulses of mechanical stimulation evoked mossy fiber responses of diminished intensity. Longer mechanical stimuli with square or ramp onsets evoked various admixtures of phasic and tonic responses. Hair stimulation was often a very effective excitant, the receptive field for a single mossy fiber usually covering a considerable area of foot and leg.Taps and pressure to the pads were also effective in inhibiting the background discharge of some mossy fibers, and admixtures of excitatory and inhibitory actions were observed.The results are discussed in relationship to the discharges evoked in primary afferent fibers by cutaneous mechanoreceptor stimulation. They provide an intermediate stage of information between mechanoreceptor stimulation and the response of Purkyně cells as described in the next paper.

The distribution to the cerebellar anterior lobe of the climbing and mossy fiber inputs from the plantar and palmar cutaneous afferents

SummarySystematic examination has been made of the potentials evoked in the ipsilateral anterior lobe by single Group II volleys in different branches of cutaneous nerves to the fore-paw and hind-paw of the cat. Field potentials evoked by the mossy and climbing fiber inputs have been recorded along microelectrode tracks arranged so that there has been a comprehensive study through the whole branching foliated structure. In a previous investigation it was shown that large cutaneous nerves of the forelimb and hindlimb have wide fields of action for both the mossy fiber and climbing fiber inputs. In this present investigation it was found that small cutaneous nerves have more localized distributions within these wide fields. This discriminative distribution is exhibited for Group II volleys in the subdivisions of the nerves providing innervation to the palmar and plantar foot pads. It thus appears from this somatotopic investigation that there are pathways to the cerebellum sufficiently specific to give information about the part of the foot that is being stimulated in natural movements.

The plasticity of the mammalian central nervous system with special reference to new growths in response to lesions

Soon after birth all generation of neurones ceases. Thereafter neuronal death takes over. We have the gloomy prospect of having inherited a brain that is progressively degenera t ing-a t least in its neuronal population. In special areas remarkable death rates occur apparently as a regulative process for neuronal populat ions that grew in excess of needs in the intial neurogenesis. For example, Cowan [1] reports that in the isthmo-optic nucleus of the chick 27000 is reduced to 11000 in a few days and in the mesencephalic nucleus 4000 reduces to 1000. In the toad Hughes [2] and Prestige [3] find a great neuronal loss in the spinal cord particularly in the motor columns. The control of neuronal death is not known nor is the basis of sparing. Presumably the neuronal multiplication in the earlier stages results in an excess of neurones and far beyond the needs of the matured neuronal system, hence the control of population by death. These are dramatic cases, but throughout the life of mammals and man there is a continuous neuronal death. Brody [4] reports that there is a continual loss of neurones in the male frontal cortex. For example the population at 40 years is reduced to half by 90 years. But fortunately, as we shall see, progressive death is not the whole story.

Brain and Free Will

That we have free will is a fact of experience. Furthermore, I state emphatically that to deny free will is neither a rational nor a logical act. This denial either presupposes free will for the deliberately chosen response in making that denial, which is a contradiction, or else it is merely the automatic response of a nervous system built by genetic coding and molded by conditioning. One does not conduct a rational argument with a being who makes the claim that all its responses are reflexes, no matter how complex and subtle the conditioning. For example, one should not argue with a Skinnerian, and moreover a Skinnerian should not engage in argument. Discourse becomes degraded into an exercise that is no more than conditioning and counter-conditioning—what we may characterize as Skinnerian games!

How Dogmatic Can Materialism Be

In the preceding paper, Dr. Savage’s technique is the classical one of erecting a straw man which he then proceeds to demolish. It would be tiresome to respond to every criticism. Instead I restrict myself to a few test cases.