Membrane bistability in olfactory bulb mitral cells (original) (raw)
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Long-lasting depolarizations in mitral cells of the rat olfactory bulb
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2000
We investigated the mechanisms of long-lasting depolarizing potentials (LLDs) generated in mitral cells with whole-cell patch recordings in the rat olfactory bulb slice. LLDs occur spontaneously and are evoked by either orthodromic stimulation of the olfactory nerve or antidromic stimulation of mitral and tufted (M/T) cells. LLDs are followed by a long refractory period, limiting LLD generation to approximately 1 Hz. LLD production does not appear to involve either intrinsic voltage-activated or metabotropic mechanisms. The initiation of LLDs requires activation of non-NMDA but not NMDA receptors. Dual recordings from the apical dendrites and somata of mitral cells show that LLDs are generated in the distal portion of the apical dendrite, most likely in the glomerulus. The rising phase of LLDs shows characteristics of polyneuronal input, including a high variability and sensitivity to charge screening. Paired recordings from adjacent mitral cells suggest that LLDs occur synchronousl...
Intrinsic oscillatory discharge patterns in mitral cells of the mouse accessory olfactory bulb
2014
Aims 2. Materials and Methods 2.1 Equipment 2.2 Consumables 2.3 Chemicals and Inhibitors 2.4 Antibodies and Sera 2.5 Solutions 2.6 Software 2.7 Animals Methods 2.8 Preparation of acute vibratome slices of AOB 2.9 Electrophysiology 2.9.1 Electrophysiological recordings from mitral cells in acute tissue slices. 2.9.2 Pulse protocols for data acquisition 2.10 Data analysis 2.11 Immunocytochemistry 2.12 Confocal imaging of biocytin-streptavidin marked cells 3. Results 3.1. Characteristics of mitral cells 3.1.1. AOB mitral cells show two different spontaneous discharge patterns Passive and active membrane properties of oscillatory and tonic mitral cells 3.1.2 Bursting properties of oscillatory mitral cells 3.1.3. Membrane potential changes do not switch oscillatory discharge into tonic in aMCs 3.1.4. Mitral cells diversity 3.2. Oscillations in extracellular recordings II 3.3. Local network independent oscillations 3.4. Ionic conductances responsible for the initiation phase of the oscillations 3.4.1. Hyperpolarization-activated cyclic nucleotide-gated current 3.4.2. Persistent sodium current 3.4.3. Extracellular calcium modulates persistent sodium current 3.4.4. Extracellular calcium modulates oscillations 3.5. Ionic conductances underlying the membrane potential upstate and action potential firing during a burst 3.
Dynamical Mechanisms of Odor Processing in Olfactory Bulb Mitral Cells
Journal of Neurophysiology, 2006
Rubin, Daniel B. and Thomas A. Cleland. Dynamical mechanisms of odor processing in olfactory bulb mitral cells. . In the olfactory system, the contribution of dynamical properties such as neuronal oscillations and spike synchronization to the representation of odor stimuli is a matter of substantial debate. While relatively simple computational models have sufficed to guide current research in large-scale network dynamics, less attention has been paid to modeling the membrane dynamics in bulbar neurons that may be equally essential to sensory processing. We here present a reduced, conductance-based compartmental model of olfactory bulb mitral cells that exhibits the complex dynamical properties observed in these neurons. Specifically, model neurons exhibit intrinsic subthreshold oscillations with voltage-dependent frequencies that shape the timing of stimulus-evoked action potentials. These oscillations rely on a persistent sodium conductance, an inactivating potassium conductance, and a calcium-dependent potassium conductance and are reset via inhibitory input such as that delivered by periglomerular cell shunt inhibition. Mitral cells fire bursts, or clusters, of spikes when continuously stimulated. Burst properties depend critically on multiple currents, but a progressive deinactivation of I A over the course of a burst is an important regulator of burst termination. Each of these complex properties exhibits appropriate dynamics and pharmacology as determined by electrophysiological studies. Additionally, we propose that a second, inconsistently observed form of infrathreshold bistability in mitral cells may derive from the activation of ATP-activated potassium currents responding to hypoxic conditions. We discuss the integration of these cellular properties in the larger context of olfactory bulb network operations.
Journal of Neurophysiology, 2001
The main olfactory bulb receives a significant modulatory noradrenergic input from the locus coeruleus. Previous in vivo and in vitro studies showed that norepinephrine (NE) inputs increase the sensitivity of mitral cells to weak olfactory inputs. The cellular basis for this action of NE is not understood. The goal of this study was to investigate the effect of NE and noradrenergic agonists on the excitability of mitral cells, the main output cells of the olfactory bulb, using whole cell patch-clamp recording in vitro. The noradrenergic agonists, phenylephrine (PE, 10 M), isoproterenol (Isop, 10 M), and clonidine (3 M), were used to test for the functional presence of ␣1-, -, and ␣2-receptors, respectively, on mitral cells. None of these agonists affected olfactory nerve (ON)-evoked field potentials recorded in the glomerular layer, or ON-evoked postsynaptic currents recorded in mitral cells. In whole cell voltage-clamp recordings, NE (30 M) induced an inward current (54 Ϯ 7 pA, n ϭ 16) with an EC 50 of 4.7 M. Both PE and Isop also produced inward currents (22 Ϯ 4 pA, n ϭ 19, and 29 Ϯ 9 pA, n ϭ 8, respectively), while clonidine produced no effect (n ϭ 6). In the presence of TTX (1 M), and blockers of excitatory and inhibitory fast synaptic transmission [gabazine 5 M, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) 10 M, and (Ϯ)-2-amino-5-phosphonopentanoic acid (APV) 50 M], the inward current induced by PE persisted (EC 50 ϭ 9 M), whereas that of Isop was absent. The effect of PE was also observed in the presence of the Ca 2ϩ channel blockers, cadmium (100 M) and nickel (100 M). The inward current caused by PE was blocked when the interior of the cell was perfused with the nonhydrolyzable GDP analogue, GDPS, indicating that the ␣1 effect is mediated by G-protein coupling. The current-voltage relationship in the absence and presence of PE indicated that the current induced by PE decreased near the equilibrium potential for potassium ions. In current-clamp recordings from bistable mitral cells, PE shifted the membrane potential from the downstate (Ϫ52 mV) toward the upstate (Ϫ40 mV), and significantly increased spike generation in response to perithreshold ON input. These findings indicate that NE excites mitral cells directly via ␣1 receptors, an effect that may underlie, at least in part, increased mitral cell responses to weak ON input during locus coeruleus activation in vivo.
European Journal of Neuroscience, 2008
In the mammalian olfactory bulb, axonless granule cells mediate self-and lateral inhibitory interactions between mitral ⁄ tufted cells via reciprocal dendrodendritic synapses. Synaptic output from granule cells occurs on both fast and slow timescales, allowing for multiple granule cell functions during olfactory processing. We find that granule cell sodium action potentials evoked by synaptic activation of the sensory input via mitral ⁄ tufted cells are followed by a long-lasting depolarization that is not observed after current-evoked action potentials or large excitatory postsynaptic potentials in the same cell. Using two-photon imaging in acute rat brain slices, we demonstrate that this prolonged electrical response is paralleled by an unusual, long-lasting postsynaptic calcium signal. We find that this slow synaptic Ca 2+ signal requires sequential activation of NMDA receptors, a nonselective cation conductance I CAN and T-type voltage-dependent Ca 2+ channels. Remarkably, T-type Ca 2+ channels are of critical importance for the 'globalization' of Ca 2+ transients. In individual active spines, the local synaptic Ca 2+ signal summates at least linearly with the global spike-mediated Ca 2+ signal. We suggest that this robust slow synaptic Ca 2+ signal triggers dendritic transmitter release and thus contributes to slow synaptic output of the granule cell. Therefore, the synaptic sodium spike signal could represent a special adaptation of granule cells to the wide range of temporal requirements for their dendritic output. Our findings demonstrate with respect to neuronal communication in general that action potentials evoked by somatic current injection may lack some of the information content of 'true' synaptically evoked spikes.
2021
In the olfactory bulb (OB), mitral cells (MCs) display a spontaneous firing that is characterized by bursts of action potentials intermixed with silent periods. Burst firing frequency and duration are heterogeneous among MCs and increase with membrane depolarization. By using patch clamp recording on rat slices, we dissected out the intrinsic properties responsible of this activity. We showed that the threshold of action potential (AP) generation dynamically changes as a function of the trajectory of the membrane potential; becoming more negative when the membrane was hyperpolarized and having a recovering rate, inversely proportional to the membrane repolarization rate. Such variations appeared to be produced by changes in the inactivation state of voltage dependent Na+ channels. Thus, the modification AP threshold favours the initiation of the burst following hyperpolarizing event such as negative membrane oscillations or inhibitory transmission. After the first AP, the following ...
Social interactions between mammalian conspecifics rely heavily on molecular communication via the main and accessory olfactory systems. These two chemosensory systems show high similarity in the organization of information flow along their early stages: social chemical cues are detected by the sensory neurons of the main olfactory epithelium and the vomeronasal organ. These neurons then convey sensory information to the main (MOB) and accessory (AOB) olfactory bulbs, respectively, where they synapse upon mitral cells that project to higher brain areas. Yet, the functional difference between these two chemosensory systems remains unclear. We have previously shown that MOB and AOB mitral cells exhibit very distinct intrinsic biophysical properties leading to different types of information processing. Specifically, we found that unlike MOB mitral cells, AOB neurons display persistent firing responses to strong stimuli. These prolonged responses are mediated by long-lasting calcium-activated non-selective cationic current (Ican). In the current study we further examined the firing characteristics of these cells and their modulation by several neuromodulators. We found that AOB mitral cells display transient depolarizing afterpotentials (DAPs) following moderate firing. These DAPs are not found in MOB mitral cells that show instead robust hyperpolarizing afterpotentials. Unlike Ican, the DAPs of AOB mitral cells are activated by low levels of intracellular calcium and are relatively insensitive to flufenamic acid. Moreover, the cholinergic agonist carbachol exerts opposite effects on the persistent firing and DAPs of AOB mitral cells. We conclude that these phenomena are mediated by distinct biophysical mechanisms that may serve to mediate different types of information processing in the AOB at distinct brain states.
Journal of Neuroscience, 2008
The initial synapse in the olfactory system is from olfactory nerve (ON) terminals to postsynaptic targets in olfactory bulb glomeruli. Recent studies have disclosed multiple presynaptic factors that regulate this important linkage, but less is known about the contribution of postsynaptic intrinsic conductances to integration at these synapses. The present study demonstrates voltage-dependent amplification of EPSPs in external tufted (ET) cells in response to monosynaptic (ON) inputs. This amplification is mainly exerted by persistent Na ϩ conductance. Larger EPSPs, which bring the membrane potential to a relatively depolarized level, are further boosted by the low-voltage-activated Ca 2ϩ conductance. In contrast, the hyperpolarization-activated nonselective cation conductance (I h) attenuates EPSPs mainly by reducing EPSP duration; this also reduces temporal summation of multiple EPSPs. Regulation of EPSPs by these subthreshold, voltage-dependent conductances can enhance both the signal-to-noise ratio and the temporal summation of multiple synaptic inputs and thus help ET cells differentiate high-and low-frequency synaptic inputs. I h can also transform inhibitory inputs to postsynaptic excitation. When the ET cell membrane potential is relatively depolarized, as during a burst of action potentials, IPSPs produce classic inhibition. However, near resting membrane potentials where I h is engaged, IPSPs produce rebound bursts of action potentials. ET cells excite GABAergic PG cells. Thus, the transformation of inhibitory inputs to postsynaptic excitation in ET cells may enhance intraglomerular inhibition of mitral/tufted cells, the main output neurons in the olfactory bulb, and hence shape signaling to olfactory cortex.
Interneurons in the olfactory bulb are key elements of odor processing but their roles have not yet being fully understood. Two types of inhibitory interneurons, periglomerular and granule cells, act at two different levels within the olfactory bulb and may have different roles in coordinating the spiking of mitral cells, which are the principal output neurons of the olfactory bulb. In this work we introduce a reduced compartmental model of the periglomerular cell and use it to investigate its role on mitral cell spiking in a model of an elementary cell triad composed of these two cell types plus a granule cell. Our simulation results show that the periglomerular cell is more effective in inhibiting the mitral cell than the granule cell. Based on our results we predict that periglomerular and granule cells have different roles in the control of mitral cell spiking. The periglomerular cell would be the only one capable of completely inhibiting the mitral cell, and the activity decrease of the mitral cell through this inhibitory action would occur in a stepwise fashion depending on parameters of the periglomerular and granule cells as well as on the relative times of arrival of external stimuli to the three cells. The major role of the granule cell would be to facilitate the inhibitory action of the periglomerular cell by enlarging the range of parameters of the periglomerular cell which correspond to complete inhibition of the mitral cell. The combined action of the two interneurons would thus provide an efficient way of controling the instantaneous value of the firing rate of the mitral cell.
Spontaneous activity of first- and second-order neurons in the frog olfactory system
Brain Research, 1994
The spontaneous activity of first-order neurons (neuroreceptors of the mucosa) and second-order neurons (mitral cells of the bulb) was recorded extracellularly in the frog olfactory system. To assess the influence of peripheral inputs upon mitral cells, the bulb was either normally connected or partially deafferented. Our first set of findings concern the firing behavior. We found that most neurons generated interspike intervals (ISis) that were stationary in mean and variance, and were not serially correlated at first and second order. Individual spikes in mitral cells and bursts of spikes in neuroreceptors were found to be generated by a Poisson process. Stochastic modeling suggests that the Poissonian behavior depends on the mean value of the membrane potential at the axon hillock. In these models, the mean potential in mitral cells would be far below the firing threshold and in neuroreceptors it would fluctuate at random between two states, one close to resting potential (between bursts) and the other close to the firing threshold with occasional crossings (within bursts). Secondly, partially deafferented mitral cells had significantly higher activity and lower variance than mitral cells receiving normal afferent input. This effect gives evidence that peripheral inputs influence mitral cells at rest not only through direct excitation but also through indirect inhibition exerted by local neurons. Thus, the unstimulated state of the olfactory bulb would not be qualitatively different from its stimulated state in the sense that both states involve the same types of synaptic interactions. Consequently, understanding the synaptic relationships that take place in the bulb network can benefit from studies of its spontaneous activity.