scholarly journals Serotonin increases synaptic activity in olfactory bulb glomeruli

2016 ◽  
Vol 115 (3) ◽  
pp. 1208-1219 ◽  
Author(s):  
Julia Brill ◽  
Zuoyi Shao ◽  
Adam C. Puche ◽  
Matt Wachowiak ◽  
Michael T. Shipley
Keyword(s):  
Olfactory Bulb ◽  
Action Potential ◽  
Sensory Input ◽  
Dynamic Range ◽  
Gaba Release ◽  
Olfactory Nerve ◽  
Synaptic Activity ◽  
Network Activity ◽  
Output Neurons ◽  
Excitatory Drive

Serotoninergic fibers densely innervate olfactory bulb glomeruli, the first sites of synaptic integration in the olfactory system. Acting through 5HT2A receptors, serotonin (5HT) directly excites external tufted cells (ETCs), key excitatory glomerular neurons, and depolarizes some mitral cells (MCs), the olfactory bulb's main output neurons. We further investigated 5HT action on MCs and determined its effects on the two major classes of glomerular interneurons: GABAergic/dopaminergic short axon cells (SACs) and GABAergic periglomerular cells (PGCs). In SACs, 5HT evoked a depolarizing current mediated by 5HT2C receptors but did not significantly impact spike rate. 5HT had no measurable direct effect in PGCs. Serotonin increased spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) in PGCs and SACs. Increased sEPSCs were mediated by 5HT2A receptors, suggesting that they are primarily due to enhanced excitatory drive from ETCs. Increased sIPSCs resulted from elevated excitatory drive onto GABAergic interneurons and augmented GABA release from SACs. Serotonin-mediated GABA release from SACs was action potential independent and significantly increased miniature IPSC frequency in glomerular neurons. When focally applied to a glomerulus, 5HT increased MC spontaneous firing greater than twofold but did not increase olfactory nerve-evoked responses. Taken together, 5HT modulates glomerular network activity in several ways: 1) it increases ETC-mediated feed-forward excitation onto MCs, SACs, and PGCs; 2) it increases inhibition of glomerular interneurons; 3) it directly triggers action potential-independent GABA release from SACs; and 4) these network actions increase spontaneous MC firing without enhancing responses to suprathreshold sensory input. This may enhance MC sensitivity while maintaining dynamic range.

scholarly journals PACAP modulation of calcium ion activity in developing granule cells of the neonatal mouse olfactory bulb

2015 ◽  
Vol 113 (4) ◽  
pp. 1234-1248 ◽  
Author(s):  
Mavis Irwin ◽  
Ann Greig ◽  
Petr Tvrdik ◽  
Mary T. Lucero
Keyword(s):  
Olfactory Bulb ◽  
Indirect Effects ◽  
Calcium Ion ◽  
Gaba Receptors ◽  
Sensory Input ◽  
Granule Cells ◽  
Gaba Release ◽  
Network Activity ◽  
Pituitary Adenylate Cyclase ◽  
Ion Activity

Ca2+ activity in the CNS is critical for the establishment of developing neuronal circuitry prior to and during early sensory input. In developing olfactory bulb (OB), the neuromodulators that enhance network activity are largely unknown. Here we provide evidence that pituitary adenylate cyclase-activating peptide (PACAP)-specific PAC1 receptors (PAC1Rs) expressed in postnatal day (P)2–P5 mouse OB are functional and enhance network activity as measured by increases in calcium in genetically identified granule cells (GCs). We used confocal Ca2+ imaging of OB slices from Dlx2-tdTomato mice to visualize GABAergic GCs. To address whether the PACAP-induced Ca2+ oscillations were direct or indirect effects of PAC1R activation, we used antagonists for the GABA receptors (GABARs) and/or glutamate receptors (GluRs) in the presence and absence of PACAP. Combined block of GABARs and GluRs yielded a 66% decrease in the numbers of PACAP-responsive cells, suggesting that 34% of OB neurons are directly activated by PACAP. Similarly, immunocytochemistry using anti-PAC1 antibody showed that 34% of OB neurons express PAC1R. Blocking either GluRs or GABARs alone indirectly showed that PACAP stimulates release of both glutamate and GABA, which activate GCs. The appearance of PACAP-induced Ca2+ activity in immature GCs suggests a role for PACAP in GC maturation. To conclude, we find that PACAP has both direct and indirect effects on neonatal OB GABAergic cells and may enhance network activity by promoting glutamate and GABA release. Furthermore, the numbers of PACAP-responsive GCs significantly increased between P2 and P5, suggesting that PACAP-induced Ca2+ activity contributes to neonatal OB development.

scholarly journals Intraglomerular inhibition shapes the strength and temporal structure of glomerular output

2012 ◽  
Vol 108 (3) ◽  
pp. 782-793 ◽  
Author(s):  
Zuoyi Shao ◽  
Adam C. Puche ◽  
Shaolin Liu ◽  
Michael T. Shipley
Keyword(s):  
Sensory Input ◽  
Granule Cells ◽  
Temporal Structure ◽  
Response Duration ◽  
Fold Increase ◽  
Gaba Release ◽  
Olfactory Nerve ◽  
Excitatory Input ◽  
Output Window ◽  
Tufted Cells

Odor signals are transmitted to the olfactory bulb by olfactory nerve (ON) synapses onto mitral/tufted cells (MCs) and external tufted cells (ETCs). ETCs, in turn, provide feedforward excitatory input to MCs. MC and ETCs are also regulated by inhibition: intraglomerular and interglomerular inhibitory circuits act at MC and ETC apical dendrites; granule cells (GCs) inhibit MC lateral dendrites via the MC→GC→MC circuit. We investigated the contribution of intraglomerular inhibition to MC and ETCs responses to ON input. ON input evokes initial excitation followed by early, strongly summating inhibitory postsynaptic currents (IPSCs) in MCs; this is followed by prolonged, intermittent IPSCs. The N-methyl-d-aspartate receptor antagonist dl-amino-5-phosphovaleric acid, known to suppress GABA release by GCs, reduced late IPSCs but had no effect on early IPSCs. In contrast, selective intraglomerular block of GABAA receptors eliminated all early IPSCs and caused a 5-fold increase in ON-evoked MC spiking and a 10-fold increase in response duration. ETCs also receive intraglomerular inhibition; blockade of inhibition doubled ETC spike responses. By reducing ETC excitatory drive and directly inhibiting MCs, intraglomerular inhibition is a key factor shaping the strength and temporal structure of MC responses to sensory input. Sensory input generates an intraglomerular excitation-inhibition sequence that limits MC spike output to a brief temporal window. Glomerular circuits may dynamically regulate this input-output window to optimize MC encoding across sniff-sampled inputs.

scholarly journals Regulation of Backpropagating Action Potentials in Mitral Cell Lateral Dendrites by A-Type Potassium Currents

2003 ◽  
Vol 89 (5) ◽  
pp. 2466-2472 ◽  
Author(s):  
J. M. Christie ◽  
G. L. Westbrook
Keyword(s):  
Olfactory Bulb ◽  
Action Potential ◽  
Action Potentials ◽  
Calcium Transient ◽  
Mitral Cell ◽  
Synaptic Activity ◽  
Calcium Transients ◽  
Access Resistance ◽  
Lateral Dendrite ◽  
Apical Dendrites

Dendrodendritic synapses, distributed along mitral cell lateral dendrites, provide powerful and extensive inhibition in the olfactory bulb. Activation of inhibition depends on effective penetration of action potentials into dendrites. Although action potentials backpropagate with remarkable fidelity in apical dendrites, this issue is controversial for lateral dendrites. We used paired somatic and dendritic recordings to measure action potentials in proximal dendritic segments (0–200 μm from soma) and action potential-generated calcium transients to monitor activity in distal dendritic segments (200–600 μm from soma). Somatically elicited action potentials were attenuated in proximal lateral dendrites. The attenuation was not due to impaired access resistance in dendrites or to basal synaptic activity. However, a single somatically elicited action potential was sufficient to evoke a calcium transient throughout the lateral dendrite, suggesting that action potentials reach distal dendritic compartments. Block of A-type potassium channels ( I A) with 4-aminopyridine (10 mM) prevented action potential attenuation in direct recordings and significantly increased dendritic calcium transients, particularly in distal dendritic compartments. Our results suggest that I A may regulate inhibition in the olfactory bulb by controlling action potential amplitudes in lateral dendrites.

scholarly journals Presynaptic gain control by endogenous cotransmission of dopamine and GABA in the olfactory bulb

2017 ◽  
Vol 117 (3) ◽  
pp. 1163-1170 ◽  
Author(s):  
Christopher E. Vaaga ◽  
Jordan T. Yorgason ◽  
John T. Williams ◽  
Gary L. Westbrook
Keyword(s):  
Olfactory Bulb ◽  
Dynamic Range ◽  
Gain Control ◽  
Gaba Release ◽  
Receptor Activation ◽  
Afferent Input ◽  
Proper Function ◽  
Endogenous Dopamine ◽  
Afferent Inputs ◽  
Tufted Cells

In the olfactory bulb, lateral inhibition mediated by local juxtaglomerular interneurons has been proposed as a gain control mechanism, important for decorrelating odorant responses. Among juxtaglomerular interneurons, short axon cells are unique as dual-transmitter neurons that release dopamine and GABA. To examine their intraglomerular function, we expressed channelrhodopsin under control of the DAT-cre promoter and activated olfactory afferents within individual glomeruli. Optical stimulation of labeled cells triggered endogenous dopamine release as measured by cyclic voltammetry and GABA release as measured by whole cell GABAA receptor currents. Activation of short axon cells reduced the afferent presynaptic release probability via D2 and GABAB receptor activation, resulting in reduced spiking in both mitral and external tufted cells. Our results suggest that short axon cells influence glomerular activity not only by direct inhibition of external tufted cells but also by inhibition of afferent inputs to external tufted and mitral cells. NEW & NOTEWORTHY Sensory systems, including the olfactory system, encode information across a large dynamic range, making synaptic mechanisms of gain control critical to proper function. Here we demonstrate that a dual-transmitter interneuron in the olfactory bulb controls the gain of intraglomerular afferent input via two distinct mechanisms, presynaptic inhibition as well as inhibition of a principal neuron subtype, and thereby potently controls the synaptic gain of afferent inputs.

scholarly journals Activation of Postsynaptic GABAB Receptors Modulates the Bursting Pattern and Synaptic Activity of Olfactory Bulb Juxtaglomerular Neurons

2008 ◽  
Vol 99 (1) ◽  
pp. 308-319 ◽  
Author(s):  
Nikolay Karpuk ◽  
Abdallah Hayar
Keyword(s):  
Olfactory Bulb ◽  
Glutamate Release ◽  
Outward Current ◽  
Olfactory Nerve ◽  
Synaptic Activity ◽  
Gabab Receptors ◽  
Channel Blockers ◽  
Potassium Channel Blockers ◽  
Olfactory Bulb Slices ◽  
Whole Cell Recordings

Olfactory bulb glomeruli are formed by a network of three major types of neurons collectively called juxtaglomerular (JG) cells, which include external tufted (ET), periglomerular (PG), and short axon (SA) cells. There is solid evidence that γ-aminobutyric acid (GABA) released from PG neurons presynaptically inhibits glutamate release from olfactory nerve terminals via activation of GABAB receptors (GABAB-Rs). However, it is still unclear whether ET cells have GABAB-Rs. We have investigated whether ET cells have functional postsynaptic GABAB-Rs using extracellular and whole cell recordings in olfactory bulb slices. In the presence of fast synaptic blockers (CNQX, APV, and gabazine), the GABAB-R agonist baclofen either completely inhibited the bursting or reduced the bursting frequency and increased the burst duration and the number of spikes/burst in ET cells. In the presence of fast synaptic blockers and tetrodotoxin, baclofen induced an outward current in ET cells, suggesting a direct postsynaptic effect. Baclofen reduced the frequency and amplitude of spontaneous EPSCs in PG and SA cells. In the presence of sodium and potassium channel blockers, baclofen reduced the frequency of miniature EPSCs, which were inhibited by the calcium channel blocker cadmium. All baclofen effects were reversed by application of the GABAB-R antagonist CGP55845 . We suggest that activation of GABAB-Rs directly inhibits ET cell bursting and decreases excitatory dendrodendritic transmission from ET to PG and SA cells. Thus the postsynaptic GABAB-Rs on ET cells may play an important role in shaping the activation pattern of the glomeruli during olfactory coding.

scholarly journals Two GABAergic Intraglomerular Circuits Differentially Regulate Tonic and Phasic Presynaptic Inhibition of Olfactory Nerve Terminals

2009 ◽  
Vol 101 (4) ◽  
pp. 1988-2001 ◽  
Author(s):  
Z. Shao ◽  
A. C. Puche ◽  
E. Kiyokage ◽  
G. Szabo ◽  
M. T. Shipley
Keyword(s):  
Olfactory Bulb ◽  
Presynaptic Inhibition ◽  
Fluorescent Protein ◽  
Gaba Release ◽  
Olfactory Nerve ◽  
Acid Decarboxylase ◽  
Nerve Terminals ◽  
Synaptic Organization ◽  
Cell Recording ◽  
Green Fluorescent

Olfactory nerve axons terminate in olfactory bulb glomeruli forming excitatory synapses onto the dendrites of mitral/tufted (M/T) and juxtaglomerular cells, including external tufted (ET) and periglomerular (PG) cells. PG cells are heterogeneous in neurochemical expression and synaptic organization. We used a line of mice expressing green fluorescent protein under the control of the glutamic acid decarboxylase 65-kDa gene (GAD65+) promoter to characterize a neurochemically identified subpopulation of PG cells by whole cell recording and subsequent morphological reconstruction. GAD65+ GABAergic PG cells form two functionally distinct populations: 33% are driven by monosynaptic olfactory nerve (ON) input (ON-driven PG cells), the remaining 67% receive their strongest drive from an ON→ET→PG circuit with no or weak monosynaptic ON input (ET-driven PG cells). In response to ON stimulation, ON-driven PG cells exhibit paired-pulse depression (PPD), which is partially reversed by GABAB receptor antagonists. The ON→ET→PG circuit exhibits phasic GABAB-R-independent PPD. ON input to both circuits is under tonic GABAB-R-dependent inhibition. We hypothesize that this tonic GABABR-dependent presynaptic inhibition of olfactory nerve terminals is due to autonomous bursting of ET cells in the ON→ET→PG circuit, which drives tonic spontaneous GABA release from ET-driven PG cells. Both circuits likely produce tonic and phasic postsynaptic inhibition of other intraglomerular targets. Thus olfactory bulb glomeruli contain at least two functionally distinct GABAergic circuits that may play different roles in olfactory coding.

Dopamine D2 Receptor–Mediated Presynaptic Inhibition of Olfactory Nerve Terminals

2001 ◽  
Vol 86 (6) ◽  
pp. 2986-2997 ◽  
Author(s):  
Matthew Ennis ◽  
Fu-Ming Zhou ◽  
Kelly J. Ciombor ◽  
Vassiliki Aroniadou-Anderjaska ◽  
Abdallah Hayar ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Dopamine D2 Receptor ◽  
Signal Transmission ◽  
D2 Receptor ◽  
Field Potential ◽  
Olfactory Nerve ◽  
D2 Receptors ◽  
Receptor Subtype ◽  
Juxtaglomerular Cells ◽  
Synaptic Responses

Olfactory receptor neurons of the nasal epithelium project via the olfactory nerve (ON) to the glomeruli of the main olfactory bulb, where they form glutamatergic synapses with the apical dendrites of mitral and tufted cells, the output cells of the olfactory bulb, and with juxtaglomerular interneurons. The glomerular layer contains one of the largest population of dopamine (DA) neurons in the brain, and DA in the olfactory bulb is found exclusively in juxtaglomerular neurons. D2 receptors, the predominant DA receptor subtype in the olfactory bulb, are found in the ON and glomerular layers, and are present on ON terminals. In the present study, field potential and single-unit recordings, as well as whole cell patch-clamp techniques, were used to investigate the role of DA and D2 receptors in glomerular synaptic processing in rat and mouse olfactory bulb slices. DA and D2 receptor agonists reduced ON-evoked synaptic responses in mitral/tufted and juxtaglomerular cells. Spontaneous and ON-evoked spiking of mitral cells was also reduced by DA and D2 agonists, and enhanced by D2 antagonists. DA did not produce measurable postsynaptic changes in juxtaglomerular cells, nor did it alter their responses to mitral/tufted cell inputs. DA also reduced 1) paired-pulse depression of ON-evoked synaptic responses in mitral/tufted and juxtaglomerular cells and 2) the amplitude and frequency of spontaneous, but not miniature, excitatory postsynaptic currents in juxtaglomerular cells. Taken together, these findings are consistent with the hypothesis that activation of D2 receptors presynaptically inhibits ON terminals. DA and D2 agonists had no effect in D2 receptor knockout mice, suggesting that D2 receptors are the only type of DA receptors that affect signal transmission from the ON to the rodent olfactory bulb.

Time course of reinnervation of the olfactory bulb after transection of the primary olfactory nerve in the pigeon

1995 ◽  
Vol 683 (2) ◽  
pp. 159-163 ◽  
Author(s):  
Roger A. Jennings ◽  
C.Jane Hambright Keiger ◽  
James C. Walker
Keyword(s):  
Olfactory Bulb ◽  
Time Course ◽  
Olfactory Nerve

Dichotomy of Action-Potential Backpropagation in CA1 Pyramidal Neuron Dendrites

2001 ◽  
Vol 86 (6) ◽  
pp. 2998-3010 ◽  
Author(s):  
Nace L. Golding ◽  
William L. Kath ◽  
Nelson Spruston
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Pyramidal Neurons ◽  
Synaptic Activity ◽  
Resting Potential ◽  
Model Parameters ◽  
Voltage Sensitivity ◽  
Whole Cell ◽  
Ca1 Pyramidal Neurons ◽  
Whole Cell Recordings

In hippocampal CA1 pyramidal neurons, action potentials are typically initiated in the axon and backpropagate into the dendrites, shaping the integration of synaptic activity and influencing the induction of synaptic plasticity. Despite previous reports describing action-potential propagation in the proximal apical dendrites, the extent to which action potentials invade the distal dendrites of CA1 pyramidal neurons remains controversial. Using paired somatic and dendritic whole cell recordings, we find that in the dendrites proximal to 280 μm from the soma, single backpropagating action potentials exhibit <50% attenuation from their amplitude in the soma. However, in dendritic recordings distal to 300 μm from the soma, action potentials in most cells backpropagated either strongly (26–42% attenuation; n = 9/20) or weakly (71–87% attenuation; n = 10/20) with only one cell exhibiting an intermediate value (45% attenuation). In experiments combining dual somatic and dendritic whole cell recordings with calcium imaging, the amount of calcium influx triggered by backpropagating action potentials was correlated with the extent of action-potential invasion of the distal dendrites. Quantitative morphometric analyses revealed that the dichotomy in action-potential backpropagation occurred in the presence of only subtle differences in either the diameter of the primary apical dendrite or branching pattern. In addition, action-potential backpropagation was not dependent on a number of electrophysiological parameters (input resistance, resting potential, voltage sensitivity of dendritic spike amplitude). There was, however, a striking correlation of the shape of the action potential at the soma with its amplitude in the dendrite; larger, faster-rising, and narrower somatic action potentials exhibited more attenuation in the distal dendrites (300–410 μm from the soma). Simple compartmental models of CA1 pyramidal neurons revealed that a dichotomy in action-potential backpropagation could be generated in response to subtle manipulations of the distribution of either sodium or potassium channels in the dendrites. Backpropagation efficacy could also be influenced by local alterations in dendritic side branches, but these effects were highly sensitive to model parameters. Based on these findings, we hypothesize that the observed dichotomy in dendritic action-potential amplitude is conferred primarily by differences in the distribution, density, or modulatory state of voltage-gated channels along the somatodendritic axis.

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