Retronasal Odor Perception Requires Taste Cortex, but Orthonasal Does Not.

Smells can arise from a source external to the body and stimulate the olfactory epithelium upon inhalation through the nares (orthonasal olfaction). Alternatively, smells may arise from inside the mouth during consumption, stimulating the epithelium upon exhalation (retronasal olfaction). Both ortho- and retronasal olfaction produce highly salient percepts, but the two percepts have very different behavioral implications. Here, we use optogenetic manipulation in the context of a flavor preference learning paradigm to investigate differences in the neural circuits that process information in these two submodalities of olfaction. Our findings support a view in which retronasal, but not orthonasal, odors share processing circuitry commonly associated with taste. First, our behavioral results reveal that retronasal odors induce rapid preference learning and have a potentiating effect on orthonasal preference learning. Second, we demonstrate that inactivation of the insular gustatory cortex selectively impairs expression of retronasal preferences. Thus, orally sourced (retronasal) olfactory input is processed by a brain region responsible for taste processing, whereas externally sourced (orthonasal) olfactory input is not.

A Multisensory Network for Olfactory Processing.

Primary gustatory cortex (GC) is connected (both mono- and polysynaptically) to primary olfactory (piriform) cortex (PC)-connections that might be hypothesized to underlie the construction of a "flavor" percept when both gustatory and olfactory stimuli are present. Here we use multisite electrophysiology and optical inhibition of GC neurons (GCx, produced via infection with ArchT) to demonstrate that, indeed, during gustatory stimulation, taste-selective information is transmitted from GC to PC. We go on to show that these connections impact olfactory processing even in the absence of gustatory stimulation: GCx alters PC responses to olfactory stimuli presented alone, enhancing some and eliminating others, despite leaving the path from nasal epithelium to PC intact. Finally, we show the functional importance of this latter phenomenon, demonstrating that GCx renders rats unable to properly recognize odor stimuli. This sequence of findings suggests that sensory processing may be more intrinsically integrative than previously thought.

Stability and flexibility of the message carried by semiochemical stimuli, as revealed by devaluation of carbon disulfide followed by social transmission of food preference.

Semiochemicals are volatile compounds that communicate specific meaning between individuals and elicit specific behavioral and/or physiological responses mediated by highly sensitive and highly specific olfactory pathways. Recent work suggests that semiochemicals can activate multiple olfactory pathways at once, but the degree to which parallel pathways activated by the same semiochemical interact and what the behavioral consequences of such interactions are remains a topic of debate. Here, we approached this question behaviorally, investigating whether rats could be trained to avoid carbon disulfide (CS2; conditional stimulus) via taste-potentiated odor aversion, and asking whether any such learning would have an impact on rats' subsequent use of CS2 as a semiochemical cue (i.e., in a socially transmitted food preference paradigm). The results show that CS2-mediated food preference learning is unimpaired by aversions conditioned to CS2, a result indicating that canonical and semiochemical pathways for the processing of CS2 function in a largely independent manner.

Deficits in glycinergic inhibition within adult spinal nociceptive circuits after neonatal tissue damage.

Tissue injury during a critical period of early postnatal development can alter pain sensitivity throughout life. However, the degree to which neonatal tissue damage exerts prolonged effects on synaptic signaling within adult spinal nociceptive circuits remains unknown. Here we provide evidence that a transient surgical injury of the hind paw during the neonatal period compromises inhibitory transmission within the adult mouse superficial dorsal horn (SDH), while the same incision occurring during the third week of life failed to evoke these long-term modifications of the SDH synaptic network. The decrease in phasic inhibitory signaling after early tissue damage reflected a selective reduction in glycine receptor (GlyR)-mediated input onto both GABAergic and presumed glutamatergic neurons within lamina II of the adult SDH. Meanwhile, neonatal incision significantly decreased the density of tonic GlyR-mediated current only in the presumed glutamatergic population during adulthood. These persistent changes in synaptic function following early injury occurred in the absence of significant alterations in the transcription of genes known to be important for glycinergic transmission. These findings suggest that aberrant sensory input during early life has permanent consequences for the functional organization of nociceptive synaptic circuits within the adult spinal cord.

Inward-rectifying potassium (Kir) channels regulate pacemaker activity in spinal nociceptive circuits during early life.

Pacemaker neurons in neonatal spinal nociceptive circuits generate intrinsic burst firing and are distinguished by a lower "leak" membrane conductance compared with adjacent nonbursting neurons. However, little is known about which subtypes of leak channels regulate the level of pacemaker activity within the developing rat superficial dorsal horn (SDH). Here we demonstrate that a hallmark feature of lamina I pacemaker neurons is a reduced conductance through inward-rectifying potassium (K(ir)) channels at physiological membrane potentials. Differences in the strength of inward rectification between pacemakers and nonpacemakers indicate the presence of functionally distinct K(ir) currents in these two populations at room temperature. However, K(ir) currents in both groups showed high sensitivity to block by extracellular Ba²âº (IC50 ~ 10 µm), which suggests the presence of "classical" K(ir) (K(ir)2.x) channels in the neonatal SDH. The reduced K(ir) conductance within pacemakers is unlikely to be explained by an absence of particular K(ir)2.x isoforms, as immunohistochemical analysis revealed the expression of K(ir)2.1, K(ir)2.2, and K(ir)2.3 within spontaneously bursting neurons. Importantly, Ba²âº application unmasked rhythmic burst firing in ∼42% of nonbursting lamina I neurons, suggesting that pacemaker activity is a latent property of a sizeable population of SDH cells during early life. In addition, the prevalence of spontaneous burst firing within lamina I was enhanced in the presence of high internal concentrations of free Mg²âº, consistent with its documented ability to block K(ir) channels from the intracellular side. Collectively, the results indicate that K(ir) channels are key modulators of pacemaker activity in newborn central pain networks.