Glutamatergic Neurons in the Piriform Cortex Influence the Activity of D1- and D2-Type Receptor-Expressing Olfactory Tubercle Neurons

Abstract

Sensory cortices process stimuli in manners essential for perception. Very little is known regarding interactions between olfactory cortices. The piriform "primary" olfactory cortex, especially its anterior division (aPCX), extends dense association fibers into the ventral striatum's olfactory tubercle (OT), yet whether this corticostriatal pathway is capable of shaping OT activity, including odor-evoked activity, is unknown. Further unresolved is the synaptic circuitry and the spatial localization of OT-innervating PCX neurons. Here we build upon standing literature to provide some answers to these questions through studies in mice of both sexes. First, we recorded the activity of OT neurons in awake mice while optically stimulating principal neurons in the aPCX and/or their association fibers in the OT while the mice were delivered odors. This uncovered evidence that PCX input indeed influences OT unit activity. We then used patchclamp recordings and viral tracing to determine the connectivity of aPCX neurons upon OT neurons expressing dopamine receptor types D1 or D2, two prominent cell populations in the OT. These investigations uncovered that both populations of neurons receive monosynaptic inputs from aPCX glutamatergic neurons. Interestingly, this input originates largely from the ventrocaudal aPCX. These results shed light on some of the basic physiological properties of this pathway and the cell-types involved and provide a foundation for future studies to identify, among other things, whether this pathway has implications for perception.

The Tubular Striatum

“…The OT also receives disynaptic input from the olfactory bulb by way of the piriform cortex (Schwob and Price, 1984a;Carriero et al, 2009; K. A. White et al, 2019), which like the OT, receives direct input from olfactory bulb output neurons. Nearly the entirety of the OT, which spans quite a large space along the ventral surface of the brain (Fig.…”

Neurochemical organization of the ventral striatum’s olfactory tubercle

“…While mitral and tufted cells may both target the OT (Igarashi et al, 2012), the majority of inputs come from tufted cells (Nagayama et al, 2010;Scott, 1981;Scott et al, 1980). Another major glutamatergic projection to the OT comes from the piriform cortex, which targets primarily the anterolateral OT (Carriero, Uva, Gnatkovsky, Curtis, & Curtis, 2009;Luskin & Price, 1983;Schwob & Price, 1984b;White et al, 2019). The bulk of this projection originates in the ventral-caudal aspect of the anterior piriform cortex (White et al, 2019) and targets all layers of the OT, with the densest fibers in layer 2 (Schwob & Price, 1984b;Schwob & Price, 1984a;White et al 2019).…”

“…Another major glutamatergic projection to the OT comes from the piriform cortex, which targets primarily the anterolateral OT (Carriero, Uva, Gnatkovsky, Curtis, & Curtis, 2009;Luskin & Price, 1983;Schwob & Price, 1984b;White et al, 2019). The bulk of this projection originates in the ventral-caudal aspect of the anterior piriform cortex (White et al, 2019) and targets all layers of the OT, with the densest fibers in layer 2 (Schwob & Price, 1984b;Schwob & Price, 1984a;White et al 2019). Aside from these major sources of glutamatergic input, midbrain dopamine (DA) neurons co-release glutamate in the OT (Mingote et al, 2015;Wieland et al, 2014).…”

“…Few studies have investigated the precise mechanisms by which glutamate neurotransmission modulates activity in the OT. White et al () explored the influence of glutamatergic input from the piriform cortex to the OT and found that optogenetic stimulation of association fiber terminals in the mouse OT modulates odor‐evoked single‐unit responses of OT neurons (White et al, ). Specifically, odor‐excited units are less excited with association fiber stimulation, while odor‐suppressed units are less suppressed with stimulation, indicating that these glutamatergic projections may influence the encoding of odors in the OT (White et al, ).…”

“…White et al () explored the influence of glutamatergic input from the piriform cortex to the OT and found that optogenetic stimulation of association fiber terminals in the mouse OT modulates odor‐evoked single‐unit responses of OT neurons (White et al, ). Specifically, odor‐excited units are less excited with association fiber stimulation, while odor‐suppressed units are less suppressed with stimulation, indicating that these glutamatergic projections may influence the encoding of odors in the OT (White et al, ). To better understand the role of glutamate co‐release from midbrain dopamine neurons, Wieland et al () recorded from CINs in acute slices while optogenetically stimulating VTA projections to the OT.…”