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J M Bower

Publications and source records attributed to J M Bower.

At least 37 records · Page 2Linked to original sources
PubMed1997

Applications of multimedia computers and video mixing to neuroethology.

Inexpensive multimedia computers offer new possibilities for mixing video and computer images, videotaping these mixed images, and extracting quantitative data from videotape. In this paper we describe methods for mixing images from a video camera and a Macintosh computer display using chroma keying, and we describe a simple circuit for analog video mixing and frame-counting. We present three applications of these video mixing methods to our neurophysiological and behavioral research with awake, behaving animals. These technologies enhance accuracy, speed, and flexibility during experiments, by allowing us to record an information-rich videotape of the subject and state of the experimental apparatus. After the experiment, these technologies facilitate selecting and extracting quantitative data from the videotape for further analysis. The videotape is especially useful in resolving minor inconsistencies or incomplete information in the notes and data files that often arise during analysis of complex experiments.

Animals↗
PubMed1997

The role of synaptic and voltage-gated currents in the control of Purkinje cell spiking: a modeling study.

We have used a realistic computer model to examine interactions between synaptic and intrinsic voltage-gated currents during somatic spiking in cerebellar Purkinje cells. We have shown previously that this model generates realistic in vivo patterns of somatic spiking in the presence of continuous background excitatory and inhibitory input (). In the present study, we analyzed the flow of synaptic and intrinsic currents across the dendritic membrane and the interaction between the soma and dendrite underlying this spiking behavior. This analysis revealed that: (1) dendritic inward current flow was dominated by a noninactivating P-type calcium current, resulting in a continuous level of depolarization; (2) the mean level of this depolarization was controlled by the mean rate of excitatory and inhibitory synaptic input; (3) the synaptic control involved a voltage-clamping mechanism exerted by changes of synaptic driving force at different membrane potentials; (4) the resulting total current through excitatory and inhibitory synapses was near-zero, with a small outward bias opposing the P-type calcium current; (5) overall, the dendrite acted as a variable current sink with respect to the soma, slowing down intrinsic inward currents in the soma; (6) the somato-dendritic current showed important phasic changes during each spike cycle; and (7) the precise timing of somatic spikes was the result of complex interactions between somatic and dendritic currents that did not directly reflect the timing of synaptic input. These modeling results suggest that Purkinje cells act quite differently from simple summation devices, as has been assumed previously in most models of cerebellar function. Specific physiologically testable predictions are discussed.

Action Potentials↗
PubMed1997

Control of sensory data acquisition.

This chapter describes a new theory of cerebellar function which posits that the cerebellum is specifically involved in monitoring and adjusting the acquisition of most of the sensory data on which the rest of the nervous system depends. If correct, the cerebellum is not itself responsible for any particular behaviorally related function, whether "motor," "sensory," or "cognitive." Instead the cerebellum facilitates the efficiency with which other brain structures perform their own functions. In this way the cerebellum is seen as being useful but not necessary for many different kinds of brain functions. This chapter describes how this theory of cerebellar function has arisen from detailed study of the pattern of tactile afferent projections to the rat cerebellum as well as from an analysis of the neural circuitry that processes that information. It is proposed that the breadth of cerebellar involvement is reflected in the growing number of tasks which induce cerebellar activity, including cognitive tasks, even though the cerebellum is not itself directly involved in those tasks.

Algorithms↗
PubMed1997

Multiday recordings from olfactory bulb neurons in awake freely moving rats: spatially and temporally organized variability in odorant response properties.

Chronic single-unit recordings were obtained from the mitral cell layer of the olfactory bulbs of awake freely moving rats placed in an odorant stream. Over periods up to five days, 618 recordings from 186 single neurons were obtained. Responses of individual neurons were found to be quite variable over time, although this variability was below chance and was not incremental. The responses of nearby neurons were more similar than expected by chance but less similar than individual neurons recorded at different times. However, responses of spatially well-separated neurons were more different than chance over short time periods. During rapid sniffing, single-unit responses became more variable, and the spatial organization of responses became less apparent. These results suggest that neuronal responses in the olfactory bulb are generally quite variable over time, with this variability increasing during periods of rapid sniffing. These results are interpreted in the context of a distributed, centrally modulated model of olfactory processing.

Animals↗
PubMed1997

The role of axonal delay in the synchronization of networks of coupled cortical oscillators.

Coupled oscillator models use a single phase variable to approximate the voltage oscillation of each neuron during repetitive firing where the behavior of the model depends on the connectivity and the interaction function chosen to describe the coupling. We introduce a network model consisting of a continuum of these oscillators that includes the effects of spatially decaying coupling and axonal delay. We derive equations for determining the stability of solutions and analyze the network behavior for two different interaction functions. The first is a sine function, and the second is derived from a compartmental model of a pyramidal cell. In both cases, the system of coupled neural oscillators can undergo a bifurcation from synchronous oscillations to waves. The change in qualitative behavior is due to the axonal delay, which causes distant connections to encourage a phase shift between cells. We suggest that this mechanism could contribute to the behavior observed in several neurobiological systems.

Axons↗
PubMed1996

Cerebellum implicated in sensory acquisition and discrimination rather than motor control.

Recent evidence that the cerebellum is involved in perception and cognition challenges the prevailing view that its primary function is fine motor control. A new alternative hypothesis is that the lateral cerebellum is not activated by the control of movement per se, but is strongly engaged during the acquisition and discrimination of sensory information. Magnetic resonance imaging of the lateral cerebellar output (dentate) nucleus during passive and active sensory tasks confirmed this hypothesis. These findings suggest that the lateral cerebellum may be active during motor, perceptual, and cognitive performances specifically because of the requirement to process sensory data.

Adult↗
PubMed1996

Contribution of somatosensory cortex to responses in the rat cerebellar granule cell layer following peripheral tactile stimulation.

The spatial coincidence of somatosensory cerebral cortex (SI) and trigeminal projections to the cerebellar hemisphere has been previously demonstrated. In this paper we describe the temporal relationship between tactilely-evoked responses in SI and in the granule cell layer of the cerebellar hemisphere, in anesthetized rats. We simultaneously recorded field potentials in areas of common receptive fields of SI and of the cerebellar folium crus IIa after peripheral tactile stimulation of the corresponding facial area. Response of the cerebellar granule cell layer to a brief tactile stimulation consisted of two components at different latencies. We found a strong correlation between the latency of the SI response and that of the second (long-latency) cerebellar component following facial stimulation. No such relationship was found between the latency of the SI response and that of the first (short-latency) cerebellar component, originating from a direct trigeminocerebellar pathway. In addition, lidocaine pressure injection in SI, cortical ablation, and decerebration all significantly affected the second cerebellar peak but not the first. Further, when tactile stimuli were presented 75 ms apart, the response in SI failed, as did the second cerebellar peak, while the short-latency cerebellar response still occurred. We found a wide spatial distribution of the upper lip response beyond the upper lip area in crus IIa for the long-latency component of the cerebellar response. Our results demonstrate that SI is the primary contributor to the cerebellar long-latency response to peripheral tactile stimulation. These results are discussed in the context of Purkinje cell responses to tactile input.

Animals↗
PubMed1995

High efficiency induction of papillomas in vivo using recombinant cottontail rabbit papillomavirus DNA.

Plasmids containing cottontail rabbit papillomavirus (CRPV) DNA can induce papillomas in vivo, but efficiency has been low. The aim of the present investigation was to explore some of the technical variables involved in inoculation of rabbits with recombinant CRPV DNA in attempts to improve both yield and consistency of papilloma induction. It was found that induction of epidermal hyperplasia, with either a mixture of turpentine and acetone or phorbol esters, produced a marked increase in papilloma yield. An additional powerful factor was the use of very vigorous, cutaneous scarification, sufficient to penetrate the papillary dermis and produce bleeding. When used in combination, papilloma yields were consistent and often reached 90-100% of inoculated sites. A number of other variables which did not consistently affect papilloma yield were tested. These included bleb and puncture injections, plasmid dose, vector type, occlusive dressings, lipofection reagent, carrier DNA, and different methods for plasmid DNA extraction and purification. It is concluded that the most important variables in improving papilloma yields were prior induction of epidermal hyperplasia and vigorous cutaneous scarification.

Acetone↗
PubMed1994

Simulated responses of cerebellar Purkinje cells are independent of the dendritic location of granule cell synaptic inputs.

Cerebellar Purkinje cell responses to granule cell synaptic inputs were examined with a computer model including active dendritic conductances. Dendritic P-type Ca2+ channels amplified postsynaptic responses when the model was firing at a physiological rate. Small synchronous excitatory inputs applied distally on the large dendritic tree resulted in somatic responses of similar size to those generated by more proximal inputs. In contrast, in a passive model the somatic postsynaptic potentials to distal inputs were 76% smaller. The model predicts that the somatic firing response of Purkinje cells is relatively insensitive to the exact dendritic location of synaptic inputs. We describe a mechanism of Ca2+-mediated synaptic amplification, based on the subspiking threshold recruitment of P-type Ca2+ channels in the dendritic branches surrounding the input site.

Animals↗
PubMed1994

Lateralization of membrane-associated protein kinase C in rat piriform cortex: specific to operant training cues in the olfactory modality.

Rats were trained on an olfactory and a control modality (auditory or visual) discrimination task and brain membrane-associated protein kinase C (mPKC) was subsequently assessed using quantitative autoradiography of radiolabelled phorbol ester binding. In rats which received olfactory-cued training, mPKC showed a highly significant lateralization in the piriform cortex but not in the hippocampus. Both olfactory-trained rats and control modality rats showed a significant increase in mPKC in the hippocampus when compared to naive rats. Thus, while behavioral training procedures appeared to result in a hippocampal increase in the activated state of this enzyme as has been reported elsewhere, only olfactory learning produced an piriform cortex lateralization in the activated state of the enzyme. While the functional significance of such a change in the distribution of protein kinase C is still unclear, it does suggest that the monitoring of this enzyme's activational state may prove to be a useful tool in the study of memory formation in a wide variety of behavioral contexts.

Animals↗
PubMed1994

Prolonged responses in rat cerebellar Purkinje cells following activation of the granule cell layer: an intracellular in vitro and in vivo investigation.

We obtained intracellular recordings of 84 Purkinje cells in vitro from guinea pig slices and of 35 cells in vivo from ketamine-anesthetized rats in order to assess detailed properties of synaptic responses in Purkinje cells following granule cell activation. In vitro, electrical stimulation of the granule cell layer underlying recorded Purkinje cells was used in sagittal slices to predominantly activate synapses on ascending granule cell axons. In vivo, stimulation of the upper lip was used to activate Purkinje cells overlying the upper lip patch in the granule cell layer of crus IIa. In the presence of a GABAA antagonist, Purkinje cells at resting membrane potential responded to both electrical stimulation in vitro and peripheral stimulation in vivo, with a depolarization of 1-10 mV amplitude that lasted for 100-300 ms in the absence of climbing fiber input. Similar prolonged depolarizations could also be induced by brief depolarizing current pulses delivered through the recording electrode, demonstrating that either synaptic or direct depolarization may activate inward currents leading to a sustained response. In support of this hypothesis we found that prolonged depolarizations were shortened significantly when stimulation in the granule cell layer or intracellular current pulses were delivered during hyperpolarizing current steps. Stimulation in the granule cell layer or intracellular current pulses delivered during periods of spontaneous somatic spiking resulted in prolonged depolarizations in dendritic recordings, which were accompanied by an increase in somatic spiking frequency. Following upper lip stimulation in vivo, this increase in somatic spiking was interrupted by an inhibition of 10-50 ms duration. In a majority of recordings, this inhibition did not completely abolish prolonged depolarizations, however, and a delayed increase in somatic spike frequency was still observed. These results suggest that prolonged increases in Purkinje cell spike frequency following peripheral stimulation are due to an underlying prolonged dendritic depolarization induced by granule cell input. Further, a single, short burst of input via ascending granule cell axons appears to be sufficient to induce these responses.

Animals↗
PubMed1994

An active membrane model of the cerebellar Purkinje cell. I. Simulation of current clamps in slice.

1. A detailed compartmental model of a cerebellar Purkinje cell with active dendritic membrane was constructed. The model was based on anatomic reconstructions of single Purkinje cells and included 10 different types of voltage-dependent channels described by Hodgkin-Huxley equations, derived from Purkinje cell-specific voltage-clamp data where available. These channels included a fast and persistent Na+ channel, three voltage-dependent K+ channels, T-type and P-type Ca2+ channels, and two types of Ca(2+)-activated K+ channels. 2. The ionic channels were distributed differentially over three zones of the model, with Na+ channels in the soma, fast K+ channels in the soma and main dendrite, and Ca2+ channels and Ca(2+)-activated K+ channels in the entire dendrite. Channel densities in the model were varied until it could reproduce Purkinje cell responses to current injections in the soma or dendrite, as observed in slice recordings. 3. As in real Purkinje cells, the model generated two types of spiking behavior. In response to small current injections the model fired exclusively fast somatic spikes. These somatic spikes were caused by Na+ channels and repolarized by the delayed rectifier. When higher-amplitude current injections were given, sodium spiking increased in frequency until the model generated large dendritic Ca2+ spikes. Analysis of membrane currents underlying this behavior showed that these Ca2+ spikes were caused by the P-type Ca2+ channel and repolarized by the BK-type Ca(2+)-activated K+ channel. As in pharmacological blocking experiments, removal of Na+ channels abolished the fast spikes and removal of Ca2+ channels removed Ca2+ spiking. 4. In addition to spiking behavior, the model also produced slow plateau potentials in both the dendrite and soma. These longer-duration potentials occurred in response to both short and prolonged current steps. Analysis of the model demonstrated that the plateau potentials in the soma were caused by the window current component of the fast Na+ current, which was much larger than the current through the persistent Na+ channels. Plateau potentials in the dendrite were carried by the same P-type Ca2+ channel that was also responsible for Ca2+ spike generation. The P channel could participate in both model functions because of the low-threshold K2-type Ca(2+)-activated K+ channel, which dynamically changed the threshold for dendritic spike generation through a negative feedback loop with the activation kinetics of the P-type Ca2+ channel. 5. These model responses were robust to changes in the densities of all of the ionic channels.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

An active membrane model of the cerebellar Purkinje cell II. Simulation of synaptic responses.

1. Both excitatory and inhibitory postsynaptic channels were added to a previously described complex compartmental model of a cerebellar Purkinje cell to examine model responses to synaptic inputs. All model parameters remained as described previously, leaving maximum synaptic conductance as the only parameter that was tuned in the studies described in this paper. Under these conditions the model was capable of reproducing physiological recorded responses to each of the major types of synaptic input. 2. When excitatory synapses were activated on the smooth dendrites of the model, the model generated a complex dendritic Ca2+ spike similar to that generated by climbing fiber inputs. Examination of the model showed that activation of P-type Ca2+ channels in both the smooth and spiny dendrites augmented the depolarization during the complex spike and that Ca(2+)-activated K+ channels in the same dendritic regions determined the duration of the spike. When these synapses were activated under simulated current-clamp conditions the model also generated the characteristic dual reversal potential of the complex spike. The shape of the dendritic complex spike could be altered by changing the maximum conductance of the climbing fiber synapse and thus the amount of Ca2+ entering the cell. 3. To explore the background simple spike firing properties of Purkinje cells in vivo we added excitatory "parallel fiber" synapses to the spiny dendritic branches of the model. Continuous asynchronous activation of these granule cell synapses resulted in the generation of spontaneous sodium spikes. However, very low asynchronous input frequencies produced a highly regular, very fast rhythm (80-120 Hz), whereas slightly higher input frequencies resulted in Purkinje cell bursting. Both types of activity are uncharacteristic of in vivo Purkinje cell recordings. 4. Inhibitory synapses of the sort presumably generated by stellate cells were also added to the dendritic tree. When asynchronous activation of these inhibitory synapses was combined with continuous asynchronous excitatory input the model generated somatic action potentials in a much more stochastic pattern typical of real Purkinje cells. Under these conditions simulated inter-spike interval distributions resembled those found in experimental recordings. Also, as with in vivo recordings, the model did not generate dendritic bursts. This was mainly due to inhibition that suppressed the generation of dendritic Ca2+ spikes. 5. In the presence of asynchronous inhibition, changes in the average frequency of excitatory inputs modulated background simple spike firing frequencies in the natural range of Purkinje cell firing frequencies (30-100 Hz). This modulation was very sensitive to small changes in the average frequency of excitatory inputs.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Microcell-mediated transfer of chromosome 6 into metastatic human C8161 melanoma cells suppresses metastasis but does not inhibit tumorigenicity.

Structural alterations of chromosome 6, including del(6q), are often associated with metastatic melanoma; therefore, we hypothesized that a metastasis-suppressor gene could be coded on human chromosome 6. Highly metastatic C8161 human malignant melanoma cells exhibit chromosomal changes typical of late-stage melanomas. Using microcell-mediated chromosome transfer, a copy of a normal human chromosome 6 was introduced into C8161. Three randomly selected hybrid clones (neo6/C8161.1, neo6/C8161.2 and neo6/C8161.3) were assayed for metastasis in athymic nude mice. All controls - parental C8161 cells, randomly-selected single cell clones, neo-transfected cell clones, neo11/C8161.2 and neo11/C8161.3 - were tumorigenic (270/272 mice) and metastatic (208/272 mice). neo6/C8161 hybrid cells were still tumorigenic (91/93 mice) but were not metastatic (0/195 mice). The presence of the added chromosomes was verified in cultured and tumor cells by amplification of polymorphic (CA)n markers using PCR-RFLP. The neo6/C8161 hybrids display growth and morphological patterns of more differentiated cells than C8161. In Northern blot analysis an inverse relationship between metastatic ability and metastasis-suppressor gene, nm23-H1, expression is observed - with clone neo6/C8161.1 expressing the highest level of nm23 transcripts, neo6/C8161.2 and neo6/C8161.3 expressing intermediate levels, and barely detectable levels are seen in C8161. Collectively, these results suggest that a malignant melanoma metastasis-regulatory gene may be located on human chromosome 6. These results further demonstrate that tumorigenicity and metastatic ability are distinct phenotypes.

Animals↗
PubMed1993

Developmental plasticity in cerebellar tactile maps: fractured maps retain a fractured organization.

Plasticity following deafferentation has been repeatedly demonstrated in topographic sensory maps in the mammalian brain. In this paper we investigated the developmental plasticity of the fractured somatotopic map found in the tactile regions of the rat cerebellum. At various stages of postnatal development between postnatal days 1 and 30, we cauterized the infraorbital branch of the trigeminal nerve, which innervates the upper lip, furry buccal pad, and vibrissae that are represented within cerebellar folium crus IIa. The organization of the crus IIa map was then examined 2 to 3 months after denervation. We found that tactile receptive fields had reorganized throughout the denervated area but maintained a fractured somatotopy. Comparison of the reorganization in different animals showed that the denervated upper lip region was consistently and predominantly replaced by representation of the upper incisors. Analysis of evoked field potentials revealed an alteration, in denervated animals, of the response of the granule cell layer to brief tactile stimulation. This response in normal animals consists of two components at different latencies. Animals lesioned later in development were less likely to have the short latency component. This result suggests a difference in the developmental sensitivity of different cerebellum-related pathways to nerve lesions.

Animals↗