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James M Bower

Publications and source records attributed to James M Bower.

13 recordsLinked to original sources

Feedforward inhibition controls the spread of granule cell-induced Purkinje cell activity in the cerebellar cortex.

Synapses associated with the parallel fiber (pf) axons of cerebellar granule cells constitute the largest excitatory input onto Purkinje cells (PCs). Although most theories of cerebellar function assume these synapses produce an excitatory sequential "beamlike" activation of PCs, numerous physiological studies have failed to find such beams. Using a computer model of the cerebellar cortex we predicted that the lack of PCs beams is explained by the concomitant pf activation of feedforward molecular layer inhibition. This prediction was tested, in vivo, by recording PCs sharing a common set of pfs before and after pharmacologically blocking inhibitory inputs. As predicted by the model, pf-induced beams of excitatory PC responses were seen only when inhibition was blocked. Blocking inhibition did not have a significant effect in the excitability of the cerebellar cortex. We conclude that pfs work in concert with feedforward cortical inhibition to regulate the excitability of the PC dendrite without directly influencing PC spiking output. This conclusion requires a significant reassessment of classical interpretations of the functional organization of the cerebellar cortex.

Action Potentials↗

Slow-waves in the olfactory system: an olfactory perspective on cortical rhythms.

Over the past few years, it has become clear that oscillatory dynamics of cortical networks are closely involved in sensory coding, attention, memory and sleep. Although most experimental and theoretical studies have focused on the neocortex, we believe that progress in understanding cortical oscillations can be advanced by also considering the olfactory system--which shares many basic properties with the neocortex and shows similar oscillatory patterns. Besides offering the advantage of a greater experimental tractability, the olfactory cortex might prove to be instrumental in uncovering general functional principles of neocortical oscillations, by virtue of the potentially important role of olfaction during neocortical evolution. In this article, we illustrate how such an evolution-based comparative approach can provide novel insights into neocortical slow-wave sleep oscillations and their relationship to respiration.

Animals↗

Topographical organization of pathways from somatosensory cortex through the pontine nuclei to tactile regions of the rat cerebellar hemispheres.

The granule cell layer of the cerebellar hemispheres contains a patchy and noncontinuous map of the body surface, consisting of a complex mosaic of multiple perioral tactile representations. Previous physiological studies have shown that cerebrocerebellar mossy fibre projections, conveyed through the pontine nuclei, are mapped in registration with peripheral tactile projections to the cerebellum. In contrast to the fractured cerebellar map, the primary somatosensory cortex (SI) is somatotopically organized. To understand better the map transformation occurring in cerebrocerebellar pathways, we injected axonal tracers in electrophysiologically defined locations in Sprague-Dawley rat folium crus IIa, and mapped the distribution of retrogradely labelled neurons within the pontine nuclei using three-dimensional (3-D) reconstructions. Tracer injections within the large central upper lip patch in crus IIa-labelled neurons located centrally in the pontine nuclei, primarily contralateral to the injected side. Larger injections (covering multiple crus IIa perioral representations) resulted in labelling extending only slightly beyond this region, with a higher density and more ipsilaterally labelled neurons. Combined axonal tracer injections in upper lip representations in SI and crus IIa, revealed a close spatial correspondence between the cerebropontine terminal fields and the crus IIa projecting neurons. Finally, comparisons with previously published three-dimensional distributions of pontine neurons labelled following tracer injections in face receiving regions in the paramedian lobule (downloaded from http://www.rbwb.org) revealed similar correspondence. The present data support the coherent topographical organization of cerebro-ponto-cerebellar networks previously suggested from physiological studies. We discuss the present findings in the context of transformations from cerebral somatotopic to cerebellar fractured tactile representations.

Animals↗

Mechanisms underlying reorganization of fractured tactile cerebellar maps after deafferentation in developing and adult rats.

Our previous studies showed that fractured tactile cerebellar maps in rats reorganize after deafferentation during development and in adulthood while maintaining a fractured somatotopy. Several months after deafferentation of the infraorbital branch of the trigeminal nerve, the missing upper lip innervation is replaced in the tactile maps in the granule cell layer of crus IIa. The predominant input into the denervated area is always the upper incisor representation. This study examined whether this reorganization was caused by mechanisms intrinsic to the cerebellum or extrinsic, i.e., occurring in somatosensory structures afferent to the cerebellum. We first compared normal and deafferented maps and found that the expansion of the upper incisor is not caused by a preexisting bias in the strength or abundance of upper incisor input in normal animals. We then mapped tactile representations before and immediately after denervation. We found that the pattern of reorganization observed in the cerebellum several months later is not caused by unmasking of a silent or weaker upper incisor representation. Both results indicate that the reorganization is not a result of subsequent growth or sprouting mechanism within the cerebellum itself. Finally, we compared postlesion maps in the cerebellum and the somatosensory cortex. We found that the upper incisor representation significantly expands in both regions and that this expansion is correlated, suggesting that reorganization in the cerebellum is a passive consequence of reorganization in afferent cerebellar pathways. This result has important developmental and functional implications.

Age Factors↗

Correlations between purkinje cell single-unit activity and simultaneously recorded field potentials in the immediately underlying granule cell layer.

Evidence from both anatomical and physiological studies suggests that the ascending segment of the granule cell axon provides a large, driving input to overlying Purkinje cells. In the current experiments, we used dual recording electrodes to simultaneously record spike activity of Purkinje cells and multiunit field potential activity in the directly underlying granule cell layer. These dual recordings were performed both during periods of spontaneous ("background") firing and also after peripheral tactile stimulation. The results demonstrate that in the large majority of cases, there is a strong positive correlation between spontaneous Purkinje cell simple spikes and spontaneous activity in the immediately underlying granule cell layer. The strength of this correlation was dependent on both the firing rate of the Purkinje cell as well as on the rate of granule cell layer multiunit activity. In addition, for any given pair of recordings, the correlation seen during spontaneous activity accurately predicted the magnitude and time course of responses evoked by peripheral tactile stimulation. These results provide additional evidence that the synapses associated with the ascending segment of the granule cell axon have a substantial influence on Purkinje cell output. This relationship is considered in the context of our ongoing reevaluation of the physiological relationship between cerebellar granule and Purkinje cells.

Action Potentials↗

Variable coupling between olfactory system activity and respiration in ketamine/xylazine anesthetized rats.

In this study, we have characterized slow and fast oscillations at several stages of olfactory processing under light and deep ketamine/xylazine anesthesia in the albino rat. While monitoring the animal's respiration, we also obtained field potentials from the olfactory bulb and piriform (olfactory) cortex and simultaneously recorded membrane potentials in piriform cortex pyramidal cells. Our results demonstrate that oscillations are generally found at higher frequencies under lighter and lower frequencies under deeper anesthesia. In previous studies of cerebral cortex, similar results in ketamine/xylazine anesthetized animals have been interpreted to correspond with the higher frequencies found during waking and lower frequencies found in the sleep state. Correlation and coherence analysis between data obtained in the bulb and cortex reveals a clear difference in coupling depending on the anesthetic state of the animal. Specifically, activity recorded in the whole system is highly correlated with respiration during deep anesthesia, whereas only the olfactory bulb, and not the cortex, is correlated with respiration during light anesthesia. These data suggest that global activity in the piriform cortex is actually more directly tied to peripheral slow respiratory input during slow wave than fast wave states and that the coupling between olfactory structures can be dynamically modulated by the level of anesthesia and therefore presumably by different brain states as well.

Analgesics↗

Cerebellum and auditory function: an ALE meta-analysis of functional neuroimaging studies.

Over the past two decades neuroimaging data have accumulated showing that the cerebellum, traditionally viewed only as a motor structure, is also active in a wide variety of sensory and cognitive tasks. We have proposed that instead of explicit involvement in any particular motor, sensory, or cognitive task, the cerebellum performs a much more fundamental computation involving the active acquisition of sensory data. We carried out an activation likelihood estimate (ALE) meta-analysis to determine whether neuroimaging results obtained during a wide range of auditory tasks support this proposal. Specifically, we analyzed the coordinates of 231 activation foci obtained in 15 different auditory studies selected through an extensive search of the positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) literature. The studies selected represent a wide variety of purely auditory tasks using highly controlled synthesized acoustic stimuli. The results clearly revealed that in addition to temporal auditory areas of cerebral cortex, specific regions in the cerebellum are activated consistently across studies regardless of the particular auditory task involved. In particular, one area in left lateral crus I area showed the greatest volume and ALE peak value among the extratemporal regions. A subanalysis was carried out that ruled out the specific association of this cerebellar cluster with attentional demand. The results are consistent with the hypothesis that the cerebellum may play a role in purely sensory auditory processing, and are discussed in light of the broader idea of the cerebellum subserving a fundamental sensory function.

Acoustic Stimulation↗

Background synaptic activity modulates the response of a modeled purkinje cell to paired afferent input.

We studied the possible effects of background excitatory and inhibitory synaptic activity on Purkinje cell responses to paired pulse inputs using a morphologically and physiologically detailed compartmental model. Paired-pulse inputs were provided via synapses associated with the ascending segment of the granule cell axon in the presence of variable amounts of background synaptic input provided by parallel fibers and inhibitory interneurons. The results predict the amplitude and dynamics of the somatic and dendritic responses to paired ascending segment inputs are modulated by the level of background synaptic activity, the basal somatic firing rate of the Purkinje cell model does not indicate the type or degree of modulation, and the modulatory effects are mediated through dendritic calcium and calcium-activated potassium currents. These results have important consequences for the functional organization of cerebellar cortex as well as the more general issue of the modulatory as distinct from driving effects of synapses now also being considered in other regions of the mammalian brain including the cerebral cortex.

Action Potentials↗

Ketamine-xylazine-induced slow (< 1.5 Hz) oscillations in the rat piriform (olfactory) cortex are functionally correlated with respiration.

The occurrence of low frequency (<1.5 Hz) cerebral cortical oscillations during slow-wave sleep has recently lead to the suggestion that this pattern of activity is specifically associated with conditions in which the brain is mostly closed to external inputs and running on its own. In the current experiments, we used a combination of in vivo intracellular and extracellular field potential recordings obtained under conditions of ketamine-xylazine anesthesia to examine slow-wave behavior in the olfactory system. We demonstrate the occurrence of low-frequency oscillations in field potentials of both the olfactory bulb and cortex and in the membrane potentials of cortical pyramidal cells. By monitoring ongoing breathing, we also show that these oscillations are all correlated with the natural breathing cycle. Using a tracheotomized preparation, we demonstrate that slow oscillatory patterns could occasionally be produced even when air is no longer entering the nose, supporting the view that the olfactory system has an intrinsic propensity to oscillate. However, in the case of tracheotomized rats, the amplitude and regularity of the oscillations as well as their patterns of correlation are disrupted. All temporal relationships were restored when air was pulsed into the nostrils. We conclude that, in the olfactory system of freely breathing rats, there is a strong relationship between the occurrence and timing of slow oscillations and the ongoing periodic sensory input resulting from respiration. This coupling between olfactory cortex slow oscillations and respiration may result from the interaction between respiratory-related rhythmic input and the tendency for olfactory structures to oscillate intrinsically. We believe this finding has important functional as well as evolutionary implications.

Animals↗

Involvement of the cerebellum in semantic discrimination: an fMRI study.

We investigated, using functional magnetic resonance imaging (fMRI), whether semantic discrimination, an inner linguistic task without overt articulation, can elicit activation in the cerebellum. Six subjects performed three semantic tasks with different loads of discrimination while being scanned. All three semantic tasks activated distributed brain areas, including the right posterior inferior cerebellum. Much stronger activation was found in the cerebellum in more difficult tasks, in terms of the activation volume and signal intensity. These results suggest that the cerebellum activation is involved in semantic discrimination and is modulated by discrimination difficulty.

Adult↗

The influence of somatosensory cortex on climbing fiber responses in the lateral hemispheres of the rat cerebellum after peripheral tactile stimulation.

This report describes the temporal relationship between the latency of responses to peripheral stimulation in primary somatosensory (SI) cerebral cortex and the timing of climbing fiber inputs to the lateral hemispheres of the rat cerebellum. Examined in the tactilely responsive regions of crus IIa in the rat, the results show that SI influences the timing of both evoked and spontaneous climbing fiber activity in these cerebellar regions without affecting the rate or probability of complex spike discharge. By reversibly blocking SI activity, we demonstrate that the absence of cortical input results in a lengthening of climbing fiber response latency to peripheral stimuli. Similarly, enhancing the cortical input by subthreshold electrical stimulation of SI results in a shortening of climbing fiber response latency. These results provide a new explanation for the tendency of the inferior olive to oscillate at 7-12 Hz and is consistent with the hypothesis that the inferior olive provides the cerebellum information about the timing of cortical computational cycles. Results are discussed in the context of previous and current hypotheses concerning the physiology and function of the inferior olive/climbing fiber system and are interpreted to provide additional evidence of a role for the cerebellum in the tactile somatosensory system.

Action Potentials↗

The organization of cerebellar cortical circuitry revisited: implications for function.

For more than 35 years there has been experimental evidence that parallel fiber activity does not generate the beams of activated Purkinje cells hypothesized on the basis of cortical anatomy and assumed by most theories of cerebellar cortical function. This paper first reviews the evidence for and against the parallel fiber beam hypothesis, and then discusses the findings of our recent experimental and model-based investigations intended to better understand parallel fiber effects on Purkinje cells. A principal conclusion of these studies is that the excitatory effects of parallel fibers on Purkinje cell dendrites are modulating and must be considered in the context of a balancing inhibitory influence provided by molecular layer interneurons to these same dendrites. It is proposed that this association of excitation and inhibition can account for the lack of beam-like effects on Purkinje cells. The paper concludes by considering the consequences of this new interpretation of cerebellar cortical circuitry for current theories of cerebellar function.

Animals↗