Processing at Primary Chemosensory Neurons

Chemosensory perception involves the detection of chemical compounds. In animals, there are 2 chemical senses: taste, and olfaction. The two are related in that they utilize ligand-gated receptors, expressed in primary sensory neurons, to detect chemical stimuli from the surrounding environment. However, the processing of these inputs is quite different in the two systems, leading to divergent roles for olfaction and taste in sensory perception. This dissertation highlights some of these differences, by looking at processing of ethologically relevant stimuli at the very peripheral receptor neurons. The work is divided into 2 parts: water sensing by the mammalian taste system, and CO₂ sensing by the Drosophila olfactory system. In Chapter 1, I talk about water sensing in the mammalian taste system. Initiation of drinking behavior relies on peripheral water detection. It is likely that this detection is mediated, at least in part, by the taste system. Here, I have shown that acid-sensing taste receptor cells (TRCs) that were previously suggested as the sensors for sour taste, also respond to water. This response is mediated by a bicarbonate-dependent molecular mechanism, likely involving the Carbonic Anhydrase enzyme family. Furthermore, optogenetic stimulation of the acid-sensing TRCs in thirsty animals induces robust licking responses towards the light source, even in the absence of water. Conversely, thirsty animals lacking functional acid-sensing TRCs show compromised discrimination between water and non-aqueous fluids. Taken together, this work reveals the cellular mechanism of water detection by the mammalian taste system. In chapter 2, I talk about CO₂ sensing in the fruit fly. The Drosophila olfactory system responds to most odors with the activation of a large subset of its olfactory receptors (ORs). This broad activation is a consequence of the ORs having affinity to multiple chemical compounds. In contrast, a small number of odors, like CO₂, elicit responses in only single ORs. These ORs are, in contrast to most ORs, very narrowly tuned, generally responding only to that one odor. It has been assumed up until now that the specificity of these unique ORs is inherited by the olfactory receptor neurons (ORNs) they are expressed in, and even in the projection neurons (PNs), that the ORNs synapse onto. I show here that CO₂, though it activates only a single OR, the GR63a/GR21a hetero-dimer complex, actually activates multiple ORN axon terminals. This activation is due to lateral excitatory connections between axon terminals of the GR63a/GR21a expressing ORNs, and at least 4 other ORN types. Focusing on one of these ORNs, Ab1B, I show the lateral connections bypass the ORN cell bodies, only driving responses at the axon terminals. Consequently, Ab1B ORN axon terminals receive 2 sources of excitatory input, a feed-forward excitation from its endogenous OR, and a lateral excitation from GR63a/GR21a. This effectively divides the ORN into 2 compartments, distinct in their odor tuning. Finally, I show that lateral excitation is a general feature of the ORN circuit by silencing the feed-forward input of another ORN class, Ab1A. The Ab1A cell body is completely silent, but the axon terminals retain odor responses from lateral excitatory inputs. Thus, there is a lateral flow of odor information between multiple ORNs of the Drosophila olfactory system.</p

Stimulus-selective lateral signaling between olfactory afferents enables parallel encoding of distinct CO₂ dynamics

An important problem in sensory processing is how lateral interactions that mediate the integration of information across sensory channels function with respect to their stimulus tunings. We demonstrate a novel form of stimulus-selective crosstalk between olfactory channels that occurs between primary olfactory receptor neurons (ORNs). Neurotransmitter release from ORNs can be driven by two distinct sources of excitation, feedforward activity derived from the odorant receptor and lateral input originating from specific subsets of other ORNs. Consequently, levels of presynaptic release can become dissociated from firing rate. Stimulus-selective lateral signaling results in the distributed representation of CO₂, a behaviorally important environmental cue that elicits spiking in only a single ORN class, across multiple olfactory channels. Different CO₂-responsive channels preferentially transmit distinct stimulus dynamics, thereby expanding the coding bandwidth for CO₂. These results generalize to additional odors and olfactory channels, revealing a subnetwork of lateral interactions between ORNs that reshape the spatial and temporal structure of odor representations in a stimulus-specific manner

Stimulus-selective lateral signaling between olfactory afferents enables parallel encoding of distinct CO₂ dynamics

An important problem in sensory processing is how lateral interactions that mediate the integration of information across sensory channels function with respect to their stimulus tunings. We demonstrate a novel form of stimulus-selective crosstalk between olfactory channels that occurs between primary olfactory receptor neurons (ORNs). Neurotransmitter release from ORNs can be driven by two distinct sources of excitation, feedforward activity derived from the odorant receptor and lateral input originating from specific subsets of other ORNs. Consequently, levels of presynaptic release can become dissociated from firing rate. Stimulus-selective lateral signaling results in the distributed representation of CO₂, a behaviorally important environmental cue that elicits spiking in only a single ORN class, across multiple olfactory channels. Different CO₂-responsive channels preferentially transmit distinct stimulus dynamics, thereby expanding the coding bandwidth for CO₂. These results generalize to additional odors and olfactory channels, revealing a subnetwork of lateral interactions between ORNs that reshape the spatial and temporal structure of odor representations in a stimulus-specific manner

The Cellular Mechanism for Water Detection in the Mammalian Taste System

Initiation of drinking behavior relies on both internal state and peripheral water detection. While central neural circuits regulating thirst have been well studied, it is still unclear how mammals recognize external water. Here we show that acid-sensing taste receptor cells (TRCs) that were previously suggested as the sour taste sensors also mediate taste responses to water. Genetic silencing of these TRCs abolished water-evoked responses in taste nerves. Optogenetic self-stimulation of acid-sensing TRCs in thirsty animals induced robust drinking responses toward light even without water. This behavior was only observed when animals were water-deprived but not under food- or salt-depleted conditions, indicating that the hedonic value of water-evoked responses is highly internal-state dependent. Conversely, thirsty animals lacking functional acid-sensing TRCs showed compromised discrimination between water and nonaqueous fluids. Taken together, this study revealed a function of mammalian acid-sensing TRCs that provide a cue for external water