Molecular Identity of Periglomerular and Short Axon Cells

Abstract

Within glomeruli, the initial sites of synaptic integration in the olfactory pathway, olfactory sensory axons terminate on dendrites of projection and juxtaglomerular (JG) neurons. JG cells form at least two major circuits: the classic intraglomerular circuit consisting of external tufted (ET) and periglomerular (PG) cells and an interglomerular circuit comprised of the long-range connections of short axon (SA) cells. We examined the projections and the synaptic inputs of identified JG cell chemotypes using mice expressing green fluorescent protein (GFP) driven by the promoter for glutamic acid decarboxylase (GAD) 65 kDa, 67 kDa, or tyrosine hydroxylase (TH). Virtually all (97%) TH+ cells are also GAD67+ and are thus DAergic–GABAergic neurons. Using a combination of retrograde tracing, whole-cell patch-clamp recording, and single-cell three-dimensional reconstruction, we show that different JG cell chemotypes contribute to distinct microcircuits within or between glomeruli. GAD65 + GABAergic PG cells ramify principally within one glomerulus and participate in uniglomerular circuits. DAergic–GABAergic cells have extensive interglomerular projections. DAergic–GABAergic SA cells comprise two subgroups. One subpopulation contacts 5–12 glomeruli and is referred to as “oligoglomerular.” Approximately one-third of these oligoglomerular DAergic SA cells receive direct olfactory nerve (ON) synaptic input, and the remaining two-thirds receive input via a disynaptic ON→ET→SA circuit. The second population of DAergic–GABAergic SA cells also disynaptic ON input and connect tens to hundreds of glomeruli in an extensive “polyglomerular” network. Although DAergic JG cells have traditionally been considered PG cells, their interglomerular connections argue that they are more appropriately classified as SA cells.

Dopaminergic Modulation of Mitral Cells and Odor Responses in the Zebrafish Olfactory Bulb

“…D 2 -dependent effects of DA may therefore modulate odorant responses on slower timescales and adapt odor processing to changes in the environment. DA-INs receiving direct sensory input (K. Kosaka and T. Kosaka, 2005;Kiyokage et al, 2010) are strategically located to generate a modulatory output signal by integration of slowly changing inputs. DA could therefore mediate similar general functions in the OB and the retina, although the mechanisms of sensory processing and their modulation by DA are most likely different.…”

“…This input is transmitted to the principal neurons, the mitral cells (MCs) (in higher vertebrates also tufted cells) and to juxtaglomerular interneurons including external tufted cells, short-axon cells, and GABAergic periglomerular cells (K. Kosaka and T. Kosaka, 2005;ParrishAungst et al, 2007;Kiyokage et al, 2010; T. Kosaka and K. Kosaka, 2011). Interneurons mediate intraglomerular and interglomerular synaptic interactions that are thought to preprocess odor representations for higher-order computations.…”

“…The only source of DA in the OB is a subpopulation of interneurons (DAINs) that have been classified as periglomerular cells or, more recently, as short-axon cells. DA-INs coexpress GABA as a neurotransmitter, receive input from sensory neurons, interact synaptically with MCs and interneurons in the same glomerulus, and project axons to other glomeruli (K. Kosaka and T. Kosaka, 2005;Parrish-Aungst et al, 2007;Kiyokage et al, 2010; T. Kosaka and K. Kosaka, 2011) (Fig. 1).…”

Signaling between periglomerular cells reveals a bimodal role for GABA in modulating glomerular microcircuitry in the olfactory bulb

“…S4; significance for increases in individual cells established by the Kolmogorov-Smirnov test for interevent intervals between sGPSCs). Whether this reflects the reported heterogeneity in glutamatergic inputs onto the PG cells (20,21) remains to be determined. For cells exhibiting a significant increase in sEPSCs, the mean sEPSC frequency increased from 1.52 ± 0.46 Hz to 11.05 ± 2.25 Hz (n = 16; P < 0.001, paired t test).…”

From progenitors to integrated neurons: Role of neurotransmitters in adult olfactory neurogenesis

“…A subpopulation of GABAergic cells express TH, the rate limiting synthetic enzyme for dopamine, and have traditionally been considered PGCs. However their interglomerular connections argue that they are more appropriately classified as short axon (SA) cells (Kiyokage et al, 2010). New dopaminergic/GABAergic SA cells are also added to the OB circuit by adult neurogenesis (De Marchis et al, 2007;Kohwi et al, 2007).…”