Long-Range GABAergic Inhibition Modulates Spatiotemporal Dynamics of the Output Neurons in the Olfactory Bulb

Villar, Pablo S.; Hu, Ruilong; Araneda, Ricardo C.

doi:10.1523/jneurosci.1498-20.2021

Cited by 27 publications

(51 citation statements)

References 123 publications

(142 reference statements)

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“…The copyright holder for this preprint this version posted October 16, 2021. ; https://doi.org/10.1101/2021.10.15.464603 doi: bioRxiv preprint and slower decay time, disynaptic stimulation of dSACs elicited IPSCs with smaller amplitude and faster decay times (clusters 3 and 1, respectively). Segregated inhibitory inputs onto GCs are supported by previous studies indicating that a subpopulation of dSACs preferentially target the distal dendrite of GCs (Eyre et al, 2008), while BF-LRGN axons are notoriously more abundant in the GCL, suggesting a perisomatic innervation of GCs (Gracia-Llanes et al, 2010;Villar et al, 2021).…”

Section: Discussionsupporting

confidence: 64%

“…GCs receive inhibitory inputs from dSACs found in the external plexiform layer (EPL-dSAC) that directly synapse onto the distal dendrites of GCs (Eyre et al, 2008), and from LRGNs of the BF, which densely innervate deeper layers in the bulb suggesting a greater influence on the somatic region of GCs (Villar et al, 2021). We reasoned that events in clusters 1 and 3 correspond to these sources of inhibition to GCs and examined this possibility by selectively activating these inhibitory inputs using optogenetics.…”

Section: Inputs To Gcs From Dsacs and Bf-lrgns Generate Ipscs With Distinct Propertiesmentioning

confidence: 99%

“…GCs receive inhibitory inputs from local deep short-axon cells (dSACs) (Pressler and Strowbridge, 2006;Eyre et al, 2008;Burton and Urban, 2015) and from long-range GABAergic neurons (LRGNs) of the BF (Gracia-Llanes et al, 2010;Nunez-Parra et al, 2013;Sanz Diez et al, 2019;Böhm et al, 2020;Hanson et al, 2020;Villar et al, 2021). Interestingly, these two sources of inhibition appear to be segregated along the proximal-distal axis of GCs, suggesting they could differentially regulate GC function.…”

Section: Introductionmentioning

confidence: 99%

“…The copyright holder for this preprint this version posted October 16, 2021. ; https://doi.org/10.1101/2021.10.15.464603 doi: bioRxiv preprint 4 innervate deeper layers of the OB, where the somas of GCs are localized, suggesting a predominant perisomatic influence in GCs (Gracia-Llanes et al, 2010;Villar et al, 2021). Furthermore, through dendrodendritic synapses with the M/TCs at their distal dendrites, GCs engage in two types of inhibitory mechanisms to regulate M/TCs activity: localized recurrent inhibition (Isaacson and Strowbridge, 1998;Mori et al, 1999;Egger et al, 2003;Shepherd, 2004), and lateral inhibition, which involves widespread activation of the distal dendrite and the inhibition of several neighboring M/TCs.…”

Section: Introductionmentioning

confidence: 99%

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Cholinergic modulation of distinct inhibitory domains in granule cells of the olfactory bulb

Villar

Teitz

et al. 2021

Preprint

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Early olfactory processing relies on a large population of inhibitory neurons in the olfactory bulb (OB), the granule cells (GCs). GCs inhibit the OB output neurons, the mitral and tufted cells (M/TCs), shaping their responses to odors both in the spatial and temporal domains, therefore, the activity of GCs is finely tuned by local and centrifugal excitatory and inhibitory inputs. While the circuit substrates underlying regulatory inputs onto GCs are well-established, how they are locally modulated remains unclear. Here, we examine the regulation of GABAergic inhibition onto GCs by acetylcholine, a main neuromodulatory transmitter released in the OB, by basal forebrain (BF) neurons. In acute brain slices from male and female mice, we show that activation of muscarinic acetylcholine receptors (mAChRs) produces opposing effects on local and centrifugal inhibition onto GCs. By using electrophysiology, laser uncaging and optogenetics we show that the kinetics of GABAergic currents in GCs could be correlated with distal and proximal spatial domains from where they originate, along the GC somatodendritic axis. Proximal inhibition from BF afferents, is suppressed by activation of M2/M4-mAChRs. In contrast, distal local inhibition from deep short axon cells (dSACs) is enhanced by activation of M3-mAChRs. Furthermore, we show that the cholinergic enhancement of distal inhibition in GCs reduces the extent of dendrodendritic inhibition in MCs. Interestingly, the excitatory cortical feedback, which also targets the proximal region of GCs, was not modulated by acetylcholine, suggesting that muscarinic activation shifts the synaptic balance towards excitation in GCs. Together, these results suggest that BF cholinergic inputs to the OB fine tune GC-mediated inhibition of M/TCs by differentially modulating the proximal and distal domains of inhibition in GCs.

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Section: Discussionsupporting

confidence: 64%

Section: Inputs To Gcs From Dsacs and Bf-lrgns Generate Ipscs With Distinct Propertiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cholinergic modulation of distinct inhibitory domains in granule cells of the olfactory bulb

Villar

Teitz

et al. 2021

Preprint

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“…Moreover, electrophysiological evidence indicate that BF GABAergic afferents innervate several types of GABAergic interneurons. These targets include granule cells and PG cells which inhibit principal neurons (Nunez-Parra et al 2013, Sanz Diez et al 2019, Hanson et al 2020, Villar et al 2021) and deep short-axon cells which inhibit granule cells and PG cells (Case et al 2017, Sanz Diez et al 2019). Thus, depending on their target BF GABAergic inputs may inhibit or disinhibit principal neurons.…”

Section: Introductionmentioning

confidence: 99%

Target-specific control of olfactory bulb periglomerular cells by GABAergic and cholinergic basal forebrain inputs

Desaintjan

2021

Preprint

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The olfactory bulb (OB), the first relay for odor processing, receives dense GABAergic and cholinergic long-range projections from basal forebrain (BF) nuclei that provide information about the internal state and behavioral context of the animal. However, the targets, impact and dynamics of these afferents are still unclear. I studied how BF synaptic inputs modulate activity in diverse subtypes of periglomerular (PG) interneurons using optogenetic stimulation and loose cell-attached or whole-cell patch-clamp recording in OB slices from adult mice. GABAergic BF inputs potently blocked PG cells firing except in a minority of calretinin-expressing cells in which GABA release elicited spiking. Parallel cholinergic projections excited a previously overlooked PG cell subtype via synaptic activation of M1 muscarinic receptors. Low frequency stimulation of the cholinergic axons drove persistent firing in these PG cells thereby increasing tonic inhibition in principal neurons. Taken together, these findings suggest that modality-specific BF inputs can orchestrate inhibition in OB glomeruli using multiple, potentially independent, inhibitory or excitatory target-specific pathways.

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Bulbar projecting subcortical GABAergic neurons send collateral branches extensively and selectively to primary olfactory cortical regions

Hook

Puché

2022

J of Comparative Neurology

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Circuit operations of the olfactory bulb are modulated by higher order projections from multiple regions, many of which are themselves targets of bulbar output. Multiple glutamatergic regions project to the olfactory bulb, including the anterior olfactory nucleus (AON), prefrontal cortex (PFC), piriform cortex (PC), entorhinal cortex (EC), and tenia tecta (TT). In contrast, only one region provides GABAergic projections to the bulb. These GABA neurons are located in the horizontal limb of the diagonal band of Broca extending posteriorly through the magnocellular preoptic nucleus to the nucleus of the lateral olfactory bulb. However, it was unclear whether bulbar projecting GABAergic neurons collaterallize projecting to other brain regions. To address this, we mapped collateral projections from bulbar projecting GABAergic neurons using intersectional strategies of viral and traditional tract tracers. This approach revealed bulbar projecting GABAergic neurons show remarkable specificity targeting other primary olfactory cortical regions exhibiting abundant collateral projections into the accessory olfactory bulb, AON, PFC, PC, and TT. The only "nonolfactory" region receiving collateral projections was sparse connectivity to the medial prefrontal orbital cortex. This suggests that basal forebrain inhibitory feedback also modulates glutamatergic feedback areas that are themselves prominent bulbar projection regions. Thus, inhibitory feedback may be simultaneously modulating both synaptic processing of olfactory information in the bulb and associational processing of olfactory information from primary olfactory cortex. We hypothesize that these olfactory GABAergic feedback neurons are a regulator of the entire olfactory system.

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Long-Range GABAergic Inhibition Modulates Spatiotemporal Dynamics of the Output Neurons in the Olfactory Bulb

Cited by 27 publications

References 123 publications

Cholinergic modulation of distinct inhibitory domains in granule cells of the olfactory bulb

Cholinergic modulation of distinct inhibitory domains in granule cells of the olfactory bulb

Target-specific control of olfactory bulb periglomerular cells by GABAergic and cholinergic basal forebrain inputs

Bulbar projecting subcortical GABAergic neurons send collateral branches extensively and selectively to primary olfactory cortical regions

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