Summary Primary gustatory cortex (GC) is connected (both mono- and poly-synaptically) 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 multi-site 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.

Summary 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 sub-modalities 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.

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.

Pacemaker neurons in neonatal spinal nociceptive circuits generate intrinsic burst-firing and are distinguished by a lower “leak” membrane conductance compared to adjacent, non-bursting 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 (Kir) channels at physiological membrane potentials. Differences in the strength of inward rectification between pacemakers and non-pacemakers indicate the presence of functionally distinct Kir currents in these two populations at room temperature. However, Kir currents in both groups showed high sensitivity to block by extracellular Ba2+ (IC50 ~ 10 µM), which suggests the presence of ‘classical’ Kir (Kir2.x) channels in the neonatal SDH. The reduced Kir conductance within pacemakers is unlikely to be explained by an absence of particular Kir2.x isoforms, as immunohistochemical analysis revealed the expression of Kir2.1, Kir2.2 and Kir2.3 within spontaneously bursting neurons. Importantly, Ba2+ application unmasked rhythmic burst-firing in ~42% of non-bursting 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 Mg2+, consistent with its documented ability to block Kir channels from the intracellular side. Collectively, the results indicate that Kir channels are key modulators of pacemaker activity in newborn central pain networks.