The functional anatomy of the normal human auditory system: responses to 0.5 and 4.0 kHz tones at varied intensities.
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Most functional imaging studies of the auditory system have employed complex stimuli. We used positron emission tomography to map neural responses to 0.5 and 4.0 kHz sine-wave tones presented to the right ear at 30, 50, 70 and 90 dB HL and found activation in a complex neural network of elements traditionally associated with the auditory system as well as non-traditional sites such as the posterior cingulate cortex. Cingulate activity was maximal at low stimulus intensities, suggesting that it may function as a gain control center. In the right temporal lobe, the location of the maximal response varied with the intensity, but not with the frequency of the stimuli. In the left temporal lobe, there was evidence for tonotopic organization: a site lateral to the left primary auditory cortex was activated equally by both tones while a second site in primary auditory cortex was more responsive to the higher frequency. Infratentorial activations were contralateral to the stimulated ear and included the lateral cerebellum, the lateral pontine tegmentum, the midbrain and the medial geniculate. Contrary to predictions based on cochlear membrane mechanics, at each intensity, 4.0 kHz stimuli were more potent activators of the brain than the 0.5 kHz stimuli. (+info)
GABAergic excitatory synapses and electrical coupling sustain prolonged discharges in the prey capture neural network of Clione limacina.
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Afterdischarges represent a prominent characteristic of the neural network that controls prey capture reactions in the carnivorous mollusc Clione limacina. Their main functional implication is transformation of a brief sensory input from a prey into a lasting prey capture response. The present study, which focuses on the neuronal mechanisms of afterdischarges, demonstrates that a single pair of interneurons [cerebral A interneuron (Cr-Aint)] is responsible for afterdischarge generation in the network. Cr-Aint neurons are electrically coupled to all other neurons in the network and produce slow excitatory synaptic inputs to them. This excitatory transmission is found to be GABAergic, which is demonstrated by the use of GABA antagonists, uptake inhibitors, and double-labeling experiments showing that Cr-Aint neurons are GABA-immunoreactive. The Cr-Aint neurons organize three different pathways in the prey capture network, which provide positive feedback necessary for sustaining prolonged spike activity. The first pathway includes electrical coupling and slow chemical transmission from the Cr-Aint neurons to all other neurons in the network. The second feedback is based on excitatory reciprocal connections between contralateral interneurons. Recurrent excitation via the contralateral cell can sustain prolonged interneuron firing, which then drives the activity of all other cells in the network. The third positive feedback is represented by prominent afterdepolarizing potentials after individual spikes in the Cr-Aint neurons. Afterdepolarizations apparently represent recurrent GABAergic excitatory inputs. It is suggested here that these afterdepolarizing potentials are produced by GABAergic excitatory autapses. (+info)
Spontaneous network activity transiently depresses synaptic transmission in the embryonic chick spinal cord.
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We examined the effects of spontaneous or evoked episodes of rhythmic activity on synaptic transmission in several spinal pathways of embryonic day 9-12 chick embryos. We compared the amplitude of synaptic potentials evoked by stimulation of the ventrolateral funiculus (VLF), the dorsal or ventral roots, before and after episodes of activity. With the exception of the short-latency responses evoked by dorsal root stimulation, the potentials were briefly potentiated and then reduced for several minutes after an episode of rhythmic activity. Their amplitude progressively recovered in the interval between successive episodes. The lack of post-episode depression in the short-latency component of the dorsal root evoked responses is probably attributable to the absence of firing in cut muscle afferents during an episode of activity. The post-episode depression of VLF-evoked potentials was mimicked by prolonged stimulation of the VLF, subthreshold for an episode of activity. By contrast, antidromically induced motoneuron firing and the accompanying calcium entry did not depress VLF-evoked potentials recorded from the stimulated ventral root. In addition, post-episode depression of VLF-evoked synaptic currents was observed in voltage-clamped spinal neurons. Collectively, these findings suggest that somatic postsynaptic activity and calcium entry are not required for the depression. We propose instead that the mechanism may involve a form of long-lasting activity-induced synaptic depression, possibly a combination of transmitter depletion and ligand-induced changes in the postsynaptic current accompanying transmitter release. This activity-dependent depression appears to be an important mechanism underlying the occurrence of spontaneous activity in developing spinal networks. (+info)
Adult subventricular zone neuronal precursors continue to proliferate and migrate in the absence of the olfactory bulb.
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Neurons continue to be born in the subventricular zone (SVZ) of the lateral ventricles of adult mice. These cells migrate as a network of chains through the SVZ and the rostral migratory stream (RMS) into the olfactory bulb (OB), where they differentiate into mature neurons. The OB is the only known target for these neuronal precursors. Here, we show that, after elimination of the OB, the SVZ and RMS persist and become dramatically larger. The proportion of dividing [bromodeoxyuridine (BrdU)-labeled] or dying (pyknotic or terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end-labeled) cells in the RMS was not significantly affected at 3 d or 3 weeks after bulbectomy (OBX). However, by 3 months after OBX, the percentage of BrdU-labeled cells in the RMS decreased by half and that of dying cells doubled. Surprisingly, the rostral migration of precursors continued along the RMS after OBX. This was demonstrated by focal microinjections of BrdU and grafts of SVZ cells carrying LacZ under the control of a neuron-specific promoter gene. Results indicate that the OB is not essential for proliferation and the directional migration of SVZ precursors. (+info)
Cellular mechanisms contributing to response variability of cortical neurons in vivo.
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Cortical neurons recorded in vivo exhibit highly variable responses to the repeated presentation of the same stimulus. To further understand the cellular mechanisms underlying this phenomenon, we performed intracellular recordings from neurons in cat striate cortex in vivo and examined the relationships between spontaneous activity and visually evoked responses. Activity was assessed on a trial-by-trial basis by measuring the membrane potential (Vm) fluctuations and spike activity during brief epochs immediately before and after the onset of an evoked response. We found that the response magnitude, expressed as a change in Vm relative to baseline, was linearly correlated with the preceding spontaneous Vm. This correlation was enhanced when the cells were hyperpolarized to reduce the activation of voltage-gated conductances. The output of the cells, expressed as spike counts and latencies, was only moderately correlated with fluctuations in the preceding spontaneous Vm. Spike-triggered averaging of Vm revealed that visually evoked action potentials arise from transient depolarizations having a rise time of approximately 10 msec. Consistent with this, evoked spike count was found to be linearly correlated with the magnitude of Vm fluctuations in the gamma (20-70 Hz) frequency band. We also found that the threshold of visually evoked action potentials varied over a range of approximately 10 mV. Examination of simultaneously recorded intracellular and extracellular activity revealed a correlation between Vm depolarization and spike discharges in adjacent cells. Together these results demonstrate that response variability is attributable largely to coherent fluctuations in cortical activity preceding the onset of a stimulus, but also to variations in action potential threshold and the magnitude of high-frequency fluctuations evoked by the stimulus. (+info)
A genetic approach to trace neural circuits.
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Mammalian nervous system function involves billions of neurons which are interconnected in a multitude of neural circuits. Here we describe a genetic approach to chart neural circuits. By using an olfactory-specific promoter, we selectively expressed barley lectin in sensory neurons in the olfactory epithelium and vomeronasal organ of transgenic mice. The lectin was transported through the axons of those neurons to the olfactory bulb, transferred to the bulb neurons with which they synapse, and transported through the axons of bulb neurons to the olfactory cortex. The lectin also was retrogradely transported from the bulb to neuromodulatory brain areas. No evidence could be obtained for adverse effects of the lectin on odorant receptor gene expression, sensory axon targeting in the bulb, or the generation or transmission of signals by olfactory sensory neurons. Transneuronal transfer was detected prenatally in the odor-sensing pathway, but only postnatally in the pheromone-sensing pathway, suggesting that odors, but not pheromones, may be sensed in utero. Our studies demonstrate that a plant lectin can serve as a transneuronal tracer when its expression is genetically targeted to a subset of neurons. This technology can potentially be applied to a variety of vertebrate and invertebrate neural systems and may be particularly valuable for mapping connections formed by small subsets of neurons and for studying the development of connectivity as it occurs in utero. (+info)
Plaque-independent disruption of neural circuits in Alzheimer's disease mouse models.
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Autosomal dominant forms of familial Alzheimer's disease (FAD) are associated with increased production of the amyloid beta peptide, Abeta42, which is derived from the amyloid protein precursor (APP). In FAD, as well as in sporadic forms of the illness, Abeta peptides accumulate abnormally in the brain in the form of amyloid plaques. Here, we show that overexpression of FAD(717V-->F)-mutant human APP in neurons of transgenic mice decreases the density of presynaptic terminals and neurons well before these mice develop amyloid plaques. Electrophysiological recordings from the hippocampus revealed prominent deficits in synaptic transmission, which also preceded amyloid deposition by several months. Although in young mice, functional and structural neuronal deficits were of similar magnitude, functional deficits became predominant with advancing age. Increased Abeta production in the context of decreased overall APP expression, achieved by addition of the Swedish FAD mutation to the APP transgene in a second line of mice, further increased synaptic transmission deficits in young APP mice without plaques. These results suggest a neurotoxic effect of Abeta that is independent of plaque formation. (+info)
Measures of degeneracy and redundancy in biological networks.
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Degeneracy, the ability of elements that are structurally different to perform the same function, is a prominent property of many biological systems ranging from genes to neural networks to evolution itself. Because structurally different elements may produce different outputs in different contexts, degeneracy should be distinguished from redundancy, which occurs when the same function is performed by identical elements. However, because of ambiguities in the distinction between structure and function and because of the lack of a theoretical treatment, these two notions often are conflated. By using information theoretical concepts, we develop here functional measures of the degeneracy and redundancy of a system with respect to a set of outputs. These measures help to distinguish the concept of degeneracy from that of redundancy and make it operationally useful. Through computer simulations of neural systems differing in connectivity, we show that degeneracy is low both for systems in which each element affects the output independently and for redundant systems in which many elements can affect the output in a similar way but do not have independent effects. By contrast, degeneracy is high for systems in which many different elements can affect the output in a similar way and at the same time can have independent effects. We demonstrate that networks that have been selected for degeneracy have high values of complexity, a measure of the average mutual information between the subsets of a system. These measures promise to be useful in characterizing and understanding the functional robustness and adaptability of biological networks. (+info)