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Cholinergic modulation of excitability in the mice olfactory bulb: effect of local application of muscarinic agonist on dopaminergic neurones
No full textConsiderable evidence exists for an extrinsic cholinergic influence in the maturation and
function of the main olfactory bulb (OB). Indeed, the presence of cholinergic centrifugal fibers
originating from the magnocellular basal forebrain nuclei has been well documented in the OB,
and it is also well established that a number of neurodegenerative disorders related to
cholinergic systems are accompanied by olfactory dysfunctions. I n this study, we addressed the
muscarinic modulation of dopaminergic (DA) neurons in the OB. For this purpose, we used
different patch-clamp techniques to localize and characterize the diverse roles of muscarinic
agonists on DA cells in a transgenic animal model expressing a reporter protein (GFP) under
the tyrosine hydroxylase promoter. When recorded in the cell attached configuration with
bicuculline and kinurenate, DA neurones were spontaneously active. Bath application of
carbachol (50 microM) in slices and in enzymatically dissociated cells reduced spike discharge
of DA cells in cell attached mode, an effect which was fully and rapidly reversible on washout of
the agonist. In whole cell configuration no effect of the agonist was observed, unless using the
perforated patch technique, suggesting the involvement of a diffusible second messenger. The
muscarinic nature of this effect on DA cell firing was confirmed by the selective M2 agonist
oxitremorine (10 microM), which was fully blocked by atropine 100 microM. The reduction of
spike discharge induced by muscarinic receptor activation results from a membrane potential
hyperpolarisation, paralleled by an outward current in voltage-clamp conditions, whereas less
clear is the effect on membrane resistance. This muscarinic effect on dopaminergic
interneurons may be important in modulating olfactory bulb output to central structures required
for driven behaviours and may be relevant to understanding mechanisms underlying the
perturbations of cholinergic inputs to cortex that occur in AIzheimer’s disease
Neurogenesis of dopaminergic neurons in the adult mammalian olfactory bulb: a possible source of cells for neural repair strategies
No full textContrary to previously held beliefs, the adult brain is in fact capable of generating new neurons that
can integrate into its complex circuitry. Recent researches have demonstrated that neurogenesis
constitutively occurs in two specific regions of the adult mammalian brain, olfactory bulb (OB) and
hippocampus. In the OB there is a significant number of dopaminergic (DA) precursors, originated
from the subventricular zone and migrated following the rostral migratory stream. The properties of
these cells have been studied with the patch-clamp technique in a transgenic animal model
expressing GFP under the tyrosine hydroxylase (TH) promoter. Using BrdU we have first
demonstrated that, in regions not normally occupied by DA neurones (mitral and extemal plexiform
layers, ML and EPL) there are cells in which the transcription of the TH gene occurs in the absence
of significant translational activity. We have studied the functional properties of these cells,
showing that they seem to reflect different degree of maturation towards the DA phenotype as they
become progressively closer to their final destination, the glomerular layer. In fact, cells in the EPL
are autorhythmic, as are mature DA neurons in the glomerular layer, whereas TH-GFP cells in the
ML are not. Furthermore, the cells in the EPL are synaptically connected to the olfactory nerve,
whereas those in the ML are not. A new technique, based on dielectrophoresis, is being developed
to sort immature DA neurones. It is hoped that these cells, present in a region easily accessible with
surgical techniques, expanded in vitro and induced to differentiate towards the DA phenotype,
could be a convenient source of neurons for cellular replacement strategies to treat
neurodegenerative diseases affecting DA systems
Neurogenesis of Dopaminergic Neurons in the Adult Mammalian Olfactory Bulb: A Possible Source of Cells for Neural Repair Strategies
No full textContrary to previously held beliefs, the adult brain is in fact capable of generating new neurons that can integrate into its complex circuitry. Recent researches have demonstrated that neurogenesis constitutively occurs in two specific regions of the adult mammalian brain, olfactory bulb (OB) and hippocampus. In the OBthere is a significant number of dopaminergic (DA) precursors, originated from the subventricular zone and migrated following the rostral migratory stream. The properties of these cells has been studied with the patch-clamp technique in a transgenic animalmodel expressing GFP under the tyrosine hydroxylase (TH) promoter. Using BrdU we have first demonstrated that, in regions not normally occupied by DA neurones (mitral and external plexiform layers, ML and EPL) there are cells in which the transcription of the TH gene occurs in the absence of significant translational activity. We have studied the functional properties of these cells, showing that they seem to reflect different degree of maturation towards the DA phenotype as they become progressively closer to their final destination, the glomerular layer. In fact, cells in the EPL are autorhythmic, as are mature DA neurons in the glomerular layer, whereas TH-GFP cells in the ML are not. Furthermore, the cells in the EPL are synaptically connected to the olfactory nerve, whereas those in the ML are not. A new technique, based on dielectrophoresis, is being developed to sort immature DA neurones. It is hoped that these cells, present in a region easily accessible with surgical techniques, expanded in vitro and induced to differentiate towards the DA phenotype, could be a convenient source of neurons for cellular replacement strategies to treat neurodegenerative diseases affecting DA systems
Maturation of adult-generated dopaminergic neurons in the mice olfactory bulb: a functional study
No full textContrary to previously held beliefs, the adult brain is in fact capable of generating new neurons
that can integrate into its complex circuitry. Recent researches have demonstrated that
neurogenesis constitutively occurs in two specific regions of the adult mammalian brain,
olfactory bulb (OB) and hippocampus. In the OB there is a significant number of dopaminergic
(DA) precursors, originated from the subventricular zone and migrated following the rostral
migratory stream. The properties of these cells have been studied with the patch-clamp
technique in a transgenic animal model expressing GFP under the tyrosine hydroxylase (TH)
promoter. Using BrdU we have first demonstrated that, in regions not normally occupied by DA
neurones (mitral and external plexiform layers, ML and EPL) there are cells in which the
transcription of the TH gene occurs in the absence of significant translational activity. We have
studied the functional properties of these cells, showing that they seem to refiect different
degrees of maturation, acquiring gradually the traits of mature DA neurones as they become
progressively closer to their final destination, the glomerular layer. ln fact, TH-GFP cells in the
ML are not autorhythmic, although they can respond with trains of action potentials to sustained
depolarisations. On the contrary, the cells in the EPL are autorhythmic, and their pace—maker
currents are the same as in mature DA neurons in the glomerular layer. Furthermore, the cells
in the EPL are synaptically connected to the olfactory nerve, whereas those in the ML are not.
Our interpretation of these data is that TH-GFP+ cells in the ML would represented adult
generated neuroblasts committed towards a DA phenotype, which have arrested their migration
waiting for a go-ahead signal from the glomerular region, possibly consequent to the
establishment of a synaptic contact with the olfactory nerve, consensus which would allow them
to complete their differentiation towards the DA phenotype and let them to reach their final
destination going across the EPL
Neurogenesis of dopaminergic neurons in the adult mammalian olfactory bulb: a possible source of cells for neural repair strategies
No full textContrary to previously held beliefs, the adult brain is in fact capable of generating new neurons that
can integrate into its complex circuitry. Recent researches have demonstrated that neurogenesis
constitutively occurs in two specific regions of the adult mammalian brain, olfactory bulb (OB) and
hippocampus. In the OB there is a significant number of dopaminergic (DA) precursors, originated
from the subventricular zone and migrated following the rostral migratory stream. The properties of
these cells have been studied with the patch-clamp technique in a transgenic animal model
expressing GFP under the tyrosine hydroxylase (TH) promoter. Using BrdU we have first
demonstrated that, in regions not normally occupied by DA neurones (mitral and extemal plexiform
layers, ML and EPL) there are cells in which the transcription of the TH gene occurs in the absence
of significant translational activity. We have studied the functional properties of these cells,
showing that they seem to reflect different degree of maturation towards the DA phenotype as they
become progressively closer to their final destination, the glomerular layer. In fact, cells in the EPL
are autorhythmic, as are mature DA neurons in the glomerular layer, whereas TH-GFP cells in the
ML are not. Furthermore, the cells in the EPL are synaptically connected to the olfactory nerve,
whereas those in the ML are not. A new technique, based on dielectrophoresis, is being developed
to sort immature DA neurones. It is hoped that these cells, present in a region easily accessible with
surgical techniques, expanded in vitro and induced to differentiate towards the DA phenotype,
could be a convenient source of neurons for cellular replacement strategies to treat
neurodegenerative diseases affecting DA systems
Cholinergic Modulation of Dopaminergic Neurons in the Mouse Olfactory Bulb
No full textConsiderable evidence exists for an extrinsic cholinergic influence in the maturation and function of the main olfactory bulb. In this study, we addressed the muscarinic modulation of dopaminergic neurons in this structure. We used different patch-clamp techniques to characterize the diverse roles of muscarinic agonists on identified dopaminergic neurons in a transgenic animal model expressing a reporter protein (green fluorescent protein) under the tyrosine hydroxylase promoter. Bath application of acetylcholine (1 mM) in slices and in enzymatically dissociated cells reduced the spontaneous firing of dopaminergic neurons recorded in cell-attached mode. In whole-cell configuration no effect of the agonist was observed, unless using the perforated patch technique, thus suggesting the involvement of a diffusible second messenger. The effect was mediated by metabotropic receptors as it was blocked by atropine and mimicked by the m2 agonist oxotremorine (10 μM). The reduction of periglomerular cell firing by muscarinic activation results from a membrane-potential hyperpolarization caused by activation of a potassium conductance. This modulation of dopaminergic interneurons may be important in the processing of sensory information and may be relevant to understand the mechanisms underlying the olfactory dysfunctions occurring in neurodegenerative diseases affecting the dopaminergic and/or cholinergic systems
Calcium-independent synaptic transmission: artifacts or facts
No full textThe release of neurotransmitters at classical chemical synapses occurs via Ca2+ influx through voltage-dependent Ca2+ channels, which are opened following depolarization of presynaptic terminals. However, owing to a persistence or increase in the amount of transmitter released in preparations containing low concentrations of Ca2+, it has been proposed that transmitter release could also occur through a Ca(2+)-independent, carrier-mediated process. On the other hand, lowering extracellular [Ca2+] can actually promote Ca2+ influx through voltage-activated Ca2+ channels via a modification of the surface potential of plasma membranes. Therefore, the proposed Ca(2+)-independent transmitter release could be re-accommodated within the framework of the Ca2+ hypothesis of synaptic transmission by taking into account the surface-charge effects
Neurogenesis in the Adult Olfactory Bulb
No full textBeing a book chapter there is no abstract. The contents is:
11.1 Historical Note
11.2 Neurogenesis.
11.2.1 Development and Role of the Subventricular Zone
11.2.2 Progression of Cell Types within the Adult Subventricular Zone
11.2.3 Regionalization of Neuronal Stem Cells
11.2.4 Timing
11.2.5 Factors Regulating Adult Neurogenesis
11.2.5.1 Cellular Niches
11.2.5.2 Intrinsic Factors
11.2.5.3 Extrinsic and Epigenetic Factors
11.2.6 The Subventricular Zone in Humans
11.3 Migration
11.3.1 The Rostral Migratory Stream
11.3.2 Signaling Driving the Migration
11.4 Differentiation
11.4.1 Life and Death of the Newly Born Cells
11.4.2 Role of Neurotransmitters
11.4.3 Granule Cells
11.4.4 Periglomerular Cells
11.5 Functional Meaning
11.6 Concluding Remarks.
Acknowledgment
Reference
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