Biomedical subjects

C Linster

Publications and source records attributed to C Linster.

At least 19 recordsLinked to original sources

PubMed2004

Characterization of the synaptic properties of olfactory bulb projections.

The olfactory bulb directly projects to several diverse telencephalic structures, but, to date, few studies have investigated the physiological characteristics of most of these areas. As an initial step towards understanding the odor processing functions of these secondary olfactory structures, we recorded evoked field potentials in response to lateral olfactory tract stimulation in vivo in urethane-anesthetized Sprague-Dawley rats in the following brain structures: anterior olfactory nucleus, ventral and dorsal tenia tecta, olfactory tubercle, anterior and posterior piriform cortex, the anterior cortical nucleus of the amygdala, and lateral entorhinal cortex. Using paired-pulse stimulation with interpulse intervals of 25-1000 ms, we observed facilitation of the response to the second pulse in every structure examined, although the degree of facilitation varied among the target structures. Additionally, pulse train stimulation at three different frequencies (40, 10 and 2 Hz) produced facilitation of evoked field potentials that also varied among target structures. We discuss the potential utility of such short-term facilitation in olfactory processing.

Animals↗

PubMed2001

Perceptual correlates of neural representations evoked by odorant enantiomers.

Spatial activation patterns within the olfactory bulb are believed to contribute to the neural representation of odorants. In this study, we attempted to predict the perceptions of odorants from their evoked patterns of neural activity in the olfactory bulb. We first describe the glomerular activation patterns evoked by pairs of odorant enantiomers based on the uptake of [(14)C]2-deoxyglucose in the olfactory bulb glomerular layer. Using a standardized data matrix enabling the systematic comparison of these spatial odorant representations, we hypothesized that the degree of similarity among these representations would predict their perceptual similarity. The two enantiomers of carvone evoked overlapping but significantly distinct regions of glomerular activity; however, the activity patterns evoked by the enantiomers of limonene and of terpinen-4-ol were not statistically different from one another. Commensurate with these data, rats spontaneously discriminated between the enantiomers of carvone, but not between the enantiomers of limonene or terpinen-4-ol, in an olfactory habituation task designed to probe differences in olfactory perception.

Animals↗

PubMed2001

Selective loss of cholinergic neurons projecting to the olfactory system increases perceptual generalization between similar, but not dissimilar, odorants.

The neuromodulator acetylcholine is thought to modulate information processing in the olfactory system. The authors used 192 IgG-saporin, a lesioning agent selective for basal forebrain cholinergic neurons, to determine whether selective lesions of cholinergic neurons projecting to the olfactory bulb and cortex affect odor perception in rats. Lesioned and sham-operated rats were tested in an olfactory generalization paradigm with sets of chemically related odorants (n-aliphatic aldehydes, acids, and alcohols). Lesioned rats generalized more between chemically similar odorants but did not differ from controls in their response to chemically unrelated odorants or in acquisition of the conditioned odor. Results show that cholinergic inputs to the olfactory system influence perceptual qualities of odorants and confirm predictions made by computational models of this system.

Acetylcholine↗

PubMed2001

Neuromodulation and the functional dynamics of piriform cortex.

Acetylcholine and norepinephrine have a number of effects at the cellular level in the piriform cortex. Acetylcholine causes a depolarization of the membrane potential of pyramidal cells and interneurons, and suppresses the action potential frequency accommodation of pyramidal cells. Acetylcholine also has strong effects on synaptic transmission, suppressing both excitatory and inhibitory synaptic transmission. At the same time as it suppresses synaptic transmission, acetylcholine enhances synaptic modification, as demonstrated by experiments showing enhancement of long-term potentiation. Norepinephrine has similar effects. In this review, we discuss some of these different cellular effects and provide functional proposals for these individual effects in the context of the putative associative memory function of this structure.

Action Potentials↗

PubMed2000

Neural activity in the horizontal limb of the diagonal band of broca can be modulated by electrical stimulation of the olfactory bulb and cortex in rats.

Previously published theoretical models of olfactory processing suggest that cholinergic modulatory inputs to the olfactory system should be regulated by neural activity in the olfactory bulb. We tested these predictions using in vivo electrophysiology in rats. We show that the activity of approximately 20% of neurons recorded in the horizontal limb of the diagonal band of Broca (HDB), which is the source of cholinergic projections to the olfactory system, can be modulated by electrical stimulation of either the lateral olfactory tract or the cell body layer of piriform cortex. These data suggest a possible physiological pathway for the proposed regulation of neural activity in the HDB by activity in the olfactory bulb or cortex.

Animals↗

PubMed2000

Size of CA1-evoked synaptic potentials is related to theta rhythm phase in rat hippocampus.

Cholinergic and GABAergic neurons projecting to the hippocampus fire with specific phase relations to theta rhythm oscillations in the electroencephalogram (EEG). To determine if this phasic input has an impact on synaptic transmission within the hippocampus, we recorded evoked population excitatory postsynaptic potential (EPSPs) during different phases of theta rhythm by using techniques similar to those described in Rudell and Fox. Synaptic potentials elicited by stimulation of region CA3 of the contralateral hippocampus were recorded in region CA1 and CA3. In these experiments, the initial slope of evoked potentials showed a change in magnitude during different phases of the theta rhythm recorded in the dentate fissure, with individual trials showing an average of 9.5% change in slope of potentials, and the average across all experiments showing a change of 7.8%. Evoked potentials were maximal 18 degrees after the positive peak of the dentate fissure theta EEG. These potentials were also smaller by 18.2% during theta as opposed to non-theta states. Phasic changes in modulation of synaptic transmission could contribute to phase precession of hippocampal place cells and could enhance storage of new sequences of activity as demonstrated by computational models.

Anesthesia↗

PubMed1999

Concentration tuning mediated by spare receptor capacity in olfactory sensory neurons: A theoretical study.

The olfactory system is capable of detecting odorants at very low concentrations. Physiological experiments have demonstrated odorant sensitivities down to the picomolar range in preparations from the sensory epithelium. However, the contemporary model for olfactory signal transduction provides that odorants bind to olfactory receptors with relatively low specificity and consequently low affinity, making this detection of low-concentration odorants theoretically difficult to understand. We employ a computational model to demonstrate how olfactory sensory neuron (OSN) sensitivity can be tuned by modulation of receptor-effector coupling and/or by other mechanisms regulating spare receptor capacity, thus resolving this conundrum. The EC10-90 intensity tuning ranges (ITRs) of whole olfactory glomeruli and postsynaptic mitral cells are considerably broader than the commensurate ITRs of individual OSNs. These data are difficult to reconcile with certain contemporary hypotheses that convergent OSNs in mammals exhibit a homogeneous population of olfactory receptors and identical tuning for odor stimuli. We show that heterogeneity in spare receptor capacities within a convergent OSN population can increase the ITR (EC10-90) of a convergent population of OSNs regardless of the presence or absence of a diversity of receptor expression within the population. The modulation of receptor-effector coupling has been observed in OSNs; other mechanisms for cellular regulation of spare receptor capacity are also highly plausible (e.g., quantitative regulation of the relative expression levels of receptor and effector proteins). We present a model illustrating that these processes can underlie both how OSNs come to exhibit high sensitivity to odorant stimuli without necessitating increased ligand-receptor binding affinities or specificities and how a population of convergent OSNs could exhibit a broader concentration sensitivity than its individual constituent neurons, even given a population expressing identical odorant receptors. The regulation of spare receptor capacity may play an important role in the olfactory system's ability to reliably detect low odor concentrations, discriminate odor intensities, and segregate this intensity information from representations of odor quality.

Algorithms↗

PubMed1999

Behavioral responses to aliphatic aldehydes can be predicted from known electrophysiological responses of mitral cells in the olfactory bulb.

For a better understanding of the encoding of odor quality in the olfactory system, it is critical to determine how electrophysiological responses to odorants are reflected in the behavioral responses to these odorants. In this article, we use a simple behavioral paradigm to show that the behavioral responses to similar odorants can be predicted from the electrophysiological responses of neurons in the olfactory bulb. Carbon chain length in aliphatic aldehydes has been used as a model for graded similarity among odorants. Recent electrophysiological experiments have shown that mitral cells in the rabbit olfactory bulb respond with similar response patterns to aliphatic aldehydes of similar chain length. On average, mitral cells responded with increased spiking activity to stimulation with two to three different aldehydes of neighboring chain length. We here show that the perception of these odorants can be predicted from the electrophysiological responses: rats that are conditioned to a given aldehyde generalize to aldehydes with one to two carbon differences in chain length from the conditioned aldehyde. When asked to discriminate between aldehydes of different chain lengths, rats learned to discriminate between any two odorants, but the rate of acquisition depended on the degree of similarity between the two odorants.

Aldehydes↗

PubMed1999

Generalization between binary odor mixtures and their components in the rat.

We have adopted a conditioning paradigm to investigate generalization between odor mixtures and components. Rats were conditioned to find a reward buried in odor-scented cups. The conditioned odor was either a mixture (O1 + O2) or a pure component (O1). Once they learned the task to criterion, they were tested in random sequence for response to that O1, O1 + O2 and to an unrelated odor (O3). Generalization was consistently the strongest from O1 to O1 + O2 or from O1 + O2 to O1. Furthermore. the degree of generalization depended on the odorants used as O1, O2, and O3. This latter finding in a particular indicates that this assay can be used to assess properties of mixtures, which could arise at either peripheral or more central locations.

Animals↗

PubMed1999

Electrical stimulation of the horizontal limb of the diagonal band of broca modulates population EPSPs in piriform cortex.

Electrical stimulation of the horizontal limb of the diagonal band of Broca (HDB) was coupled with recording of evoked potentials in the piriform cortex. Stimulation of the HDB caused an enhancement of the late, disynaptic component of the evoked potential elicited by stimulation of the lateral olfactory tract but caused a suppression of the synaptic potential elicited by stimulation of the posterior piriform cortex. The muscarinic antagonist scopolamine blocked both effects of HDB stimulation. The enhancement of disynaptic potentials could be due to cholinergic depolarization of pyramidal cells, whereas the suppression of potentials evoked by posterior piriform stimulation could be due to presynaptic inhibition of intrinsic fiber synaptic transmission by acetylcholine.

Animals↗

PubMed1998

Glutamate and synaptic plasticity at mammalian primary olfactory synapses.

Glutamate is the transmitter at synapses from the olfactory nerve (ON) to mitral (Mi)/tufted cells, but very little is known about the functional properties of this synapse. This report summarizes in vitro physiological and computational modeling studies investigating glutamatergic neurotransmission at ON-->Mi cell synapses. Single ON shocks in rat main olfactory bulb (MOB) slices elicit distinct early and late spiking components triggered, respectively, by (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)/kainic acid (KA) and N-methyl-D-aspartate (NMDA) receptor activation. Modeling simulations showed that the placement of both AMPA/KA and NMDA receptors on Mi apical dendrites replicates the experimentally observed early and late Mi spiking responses to ON shocks. Brief, tetanic ON stimulation in vitro induced robust, selective long-term potentiation (LTP) of NMDA receptor-dependent spiking. Modeling experiments disclosed several potential mechanisms underlying the selective LTP of NMDA receptor-dependent spiking. These findings demonstrate that ON-->Mi cell transmission exhibits a novel form of plasticity whereby high frequency synaptic activity induces selective LTP of NMDA receptor-dependent spiking.

Animals↗

PubMed1998

Computational models of neuromodulation.

Computational modeling of neural substrates provides an excellent theoretical framework for the understanding of the computational roles of neuromodulation. In this review, we illustrate, with a large number of modeling studies, the specific computations performed by neuromodulation in the context of various neural models of invertebrate and vertebrate preparations. We base our characterization of neuromodulations on their computational and functional roles rather than on anatomical or chemical criteria. We review the main framework in which neuromodulation has been studied theoretically (central pattern generation and oscillations, sensory processing, memory and information integration). Finally, we present a detailed mathematical overview of how neuromodulation has been implemented at the single cell and network levels in modeling studies. Overall, neuromodulation is found to increase and control computational complexity.

Animals↗

PubMed1998

Cholinergic agonist carbachol enables associative long-term potentiation in piriform cortex slices.

Pyramidal cells in piriform (olfactory) cortex receive afferent input from the olfactory bulb as well as intrinsic association input from piriform cortex and other cortical areas. These two functionally distinct inputs terminate on adjacent apical dendritic segments of the pyramidal cells located in layer Ia and layer Ib of piriform cortex. Studies with bath-applied cholinergic agonists have shown suppression of the fast component of the inhibitory postsynaptic potentials (IPSPs) evoked by stimulation of the association fibers. It was previously demonstrated that an associative form of LTP can be induced by coactivation of the two fiber systems after blockade of the fast, gamma-aminobutyric acid-A-mediated IPSP. In this report, we demonstrate that an associative form of long-term potentiation can be induced by coactivation of afferent and intrinsic fibers in the presence of the cholinergic agonist carbachol.

Afferent Pathways↗

PubMed1997

A computational model of the response of honey bee antennal lobe circuitry to odor mixtures: overshadowing, blocking and unblocking can arise from lateral inhibition.

Recent studies of learning about elements of odorant mixtures in honey bees identified several types of interactions between mixture components, such as overshadowing and blocking. The latter phenomenon in particular indicates at least a limited ability of subjects to identify the most salient element of a binary mixture. Here we show that the circuitry in the antennal lobes, the first neuropil in which synaptic interaction affects sensory processing, could give rise to both effects given the incorporation of modifiable synapses onto inhibitory circuitry. The neural model of the antennal lobe that we present incorporates identified cell types and includes a biologically realistic modulatory neuron with which modifiable Hebb-like synaptic interactions take place. A learning rule that incorporates modifiable connections from output (projection) neurons onto the modulatory neuron is sufficient to account for behavioral results on generalization and overshadowing. A second type of excitatory connection from the modulatory neuron onto local inhibitory interneurons is necessary to reproduce behavioral results from blocking and unblocking. We suggest that the neural representations of odor mixtures in the antennal lobe can be modified by previous exposure to one of the mixture components. These results provide testable hypotheses that will guide future behavioral and physiological analyses.

Algorithms↗

PubMed1997

Modulation of inhibition in a model of olfactory bulb reduces overlap in the neural representation of olfactory stimuli.

In a neural model of olfactory bulb processing, we demonstrate the putative role of the modulation of two types of inhibition, inspired by electrophysiological data on the effect of acetylcholine and noradrenaline on olfactory bulb synaptic transmission. Feedback regulation of modulation based on bulbar activity serves to 'normalize' the activity of output neurons in response to different levels of input activities. This mechanism also decreases the overlap between pairs of output patterns (Mitral cell activities), enhancing the discrimination between overlapping olfactory input patterns. The effect of the modulation at the two levels of interneurons is complementary: while an increase in periglomerular inhibition decreases the number of responding output neurons, a decrease in granule cell inhibition increases the firing frequencies of these neurons.

Computer Simulation↗

PubMed1997

Noradrenergic suppression of synaptic transmission may influence cortical signal-to-noise ratio.

Norepinephrine has been proposed to influence signal-to-noise ratio within cortical structures, but the exact cellular mechanisms underlying this influence have not been described in detail. Here we present data on a cellular effect of norepinephrine that could contribute to the influence on signal-to-noise ratio. In brain slice preparations of the rat piriform (olfactory) cortex, perfusion of norepinephrine causes a dose-dependent suppression of excitatory synaptic potentials in the layer containing synapses among pyramidal cells in the cortex (layer Ib), while having a weaker effect on synaptic potentials in the afferent fiber layer (layer Ia). Effects of norepinephrine were similar in dose-response characteristics and laminar selectivity to the effects of the cholinergic agonist carbachol, and combined perfusion of both agonists caused effects similar to an equivalent concentration of a single agonist. In a computational model of the piriform cortex, we have analyzed the effect of noradrenergic suppression of synaptic transmission on signal-to-noise ratio. The selective suppression of excitatory intrinsic connectivity decreases the background activity of modeled neurons relative to the activity of neurons receiving direct afferent input. This can be interpreted as an increase in signal-to-noise ratio, but the term noise does not accurately characterize activity dependent on the intrinsic spread of excitation, which would more accurately be described as interpretation or retrieval. Increases in levels of norepinephrine mediated by locus coeruleus activity appear to enhance the influence of extrinsic input on cortical representations, allowing a pulse of norepinephrine in an arousing context to mediate formation of memories with a strong influence of environmental variables.

Acetylcholine↗

PubMed1996

Investigation of the role of interneurons and their modulation by centrifugal fibers in a neural model of the olfactory bulb.

Olfactory bulb processing results from the interaction of relay neurons with two main categories of interneurons which mediate inhibition in two distinct layers: periglomerular cells and granule cells. We present here a neural model of the mammalian olfactory bulb which allows to separately investigate the functional consequences of the two types of interneurons onto the relay neurons responsiveness to odors. The model, although built with simplified representations of neural elements generates various aspects of neural dynamics from the cellular to the populational level. We propose that the combined action of centrifugal control at two different layers of processing is complementary: reduction of the number of active relay neurons responding to a given odorant through increased activity of periglomerular cells, and an increase of response intensity of active mitral cells through decrease of granule cell inhibition.

Animals↗

PubMed1996

A model for pheromone discrimination in the insect antennal lobe: investigation of the role of neuronal response pattern complexity.

Based on anatomical and physiological data pertaining to several moth species and the cockroach, we propose a neural model for pheromone discrimination in the insect antennal lobe. The model exploits the variety of neuronal response patterns observed in the macroglomerulus, and predicts how these complex patterns of excitation and inhibition can participate in the discrimination of the species-specific pheromone blend. The model also allows us to investigate the relationship between the distribution of observed response patterns and the neural organization from which these patterns emerge.

Action Potentials↗