ASH sensory neurons are required in Caenorhabditis elegans for a wide range of avoidance behaviors in response to chemical repellents, high osmotic solutions and nose touch. The ASH neurons are therefore hypothesized to be polymodal nociceptive neurons. To understand the nature of polymodal sensory response and adaptation at the cellular level, we expressed the calcium indicator protein cameleon in ASH and analyzed intracellular Ca 2 þ responses following stimulation with chemical repellents, osmotic shock and nose touch. We found that a variety of noxious stimuli evoked strong responses in ASH including quinine, denatonium, detergents, heavy metals, both hyper-and hypo-osmotic shock and nose touch. We observed that repeated chemical stimulation led to a reversible reduction in the magnitude of the sensory response, indicating that adaptation occurs within the ASH sensory neuron. A key component of ASH adaptation is GPC-1, a G-protein c-subunit expressed specifically in chemosensory neurons. We hypothesize that G-protein c-subunit heterogeneity provides a mechanism for repellent-specific adaptation, which could facilitate discrimination of a variety of repellents by these polymodal sensory neurons.

by the fat (fatty acid desaturase) and elo (fatty acid and Jennifer L. Watts 4, * elongation) genes. A gas chromatography (GC)-based 1 Neuroscience Graduate Program genetic screen led to the identification of the fat and elo 2 HHMI and Department of Anatomy mutations, which disrupt the synthesis of long chain 513 Parnassus PUFAs from dietary precursors (Figure 1A) (Watts and

G protein-coupled receptors (GPCRs) mediate diverse signaling processes, including olfaction. G protein-coupled receptor kinases (GRKs) are important regulators of G protein signal transduction that specifically phosphorylate activated GPCRs to terminate signaling. Despite previously described roles for GRKs in GPCR signal downregulation, animals lacking C. elegans G protein-coupled receptor kinase-2 (Ce-grk-2) function are not hypersensitive to odorants. Instead, decreased Ce-grk-2 function in adult sensory neurons profoundly disrupts chemosensation, based on both behavioral analysis and Ca(2+) imaging. Although mammalian arrestin proteins cooperate with GRKs in receptor desensitization, loss of C. elegans arrestin-1 (arr-1) does not disrupt chemosensation. Either overexpression of the C. elegans Galpha subunit odr-3 or loss of eat-16, which encodes a regulator of G protein signaling (RGS) protein, restores chemosensation in Ce-grk-2 mutants. These results demonstrate that loss of GRK function can lead to reduced GPCR signal transduction and suggest an important role for RGS proteins in the regulation of chemosensation.

Mammalian neuronal DEG/ENaC channels known as ASICs (acid-sensing ion channels) mediate sensory perception and memory formation. ASICS are closed at rest and are gated by protons. Members of the DEG/ENaC family expressed in epithelial tissues are called ENaCs and mediate Na þ transport across epithelia. ENaCs exhibit constitutive activity and strict Na þ selectivity. We report here the analysis of the first DEG/ENaC in Caenorhabditis elegans with functional features of ENaCs that is involved in sensory perception. ACD-1 (acid-sensitive channel, degenerin-like) is constitutively open and impermeable to Ca 2 þ , yet it is required with neuronal DEG/ENaC channel DEG-1 for acid avoidance and chemotaxis to the amino acid lysine. Surprisingly, we document that ACD-1 is required in glia rather than neurons to orchestrate sensory perception. We also report that ACD-1 is inhibited by extracellular and intracellular acidification and, based on the analysis of an acid-hypersensitive ACD-1 mutant, we propose a mechanism of action of ACD-1 in sensory responses based on its sensitivity to protons. Our findings suggest that channels with ACD-1 features may be expressed in mammalian glia and have important functions in controlling neuronal function.

In the auditory cortex (AC), interhemispheric communication is involved in sound localization processes underlying spatial hearing. However, the neuronal microcircuits recruited by the callosal projections are unknown. We addressed this fundamental question by taking advantage of optogenetics and examining directly the functional effects of interhemispheric inputs to specific pyramidal neurons in layer 5 of the mouse AC, defined by their output as either corticocortical (CCort) or corticocollicular (CCol). We found that callosal projections suppress the activity of CCort pyramidal neurons, but facilitate firing of CCol pyramidal neurons. This difference is mechanistically explained by callosal activation of fast-spiking parvalbumin-expressing interneurons (FS-PARV), which provide selective inhibition to CCort pyramidal neurons. Our results establish two distinct previously unknown cortical circuits underlying either callosal suppression (callosal projections ¡ FS-PARV ¡ CCort) or facilitation (callosal projections ¡ CCol) of projecting neurons in layer 5 of the AC and attribute a specific function to a genetically defined type of interneuron in interhemispheric communication.

In motor cortex, long-range output to subcortical motor circuits depends on excitatory and inhibitory inputs converging on projection neurons in layers 5A/B. How interneurons interconnect with these projection neurons, and whether these microcircuits are interneuron- and/or projection-specific, is unclear. We found that fast spiking (FS) interneurons received strong intralaminar (horizontal) excitation from pyramidal neurons in layers 5A/B including corticostriatal and corticospinal neurons, implicating them in mediating disynaptic recurrent, feedforward, and feedback inhibition within and across the two projection classes. Low threshold spiking (LTS) interneurons were instead strongly excited by descending interlaminar (vertical) input from layer 2/3 pyramidal neurons, implicating them in mediating disynaptic feedforward inhibition to both projection classes. Furthermore, in a novel pattern, lower layer 2/3 preferentially excited interneurons in one layer (5A/LTS) and excitatory neurons in another (5B/corticospinal). Thus, these inhibitory microcircuits in mouse motor cortex follow an orderly arrangement that is laminarly orthogonalized by interneuron-specific, projection-nonspecific connectivity.

Anatomical and physiological studies have led to the assumption that the dorsal striatum receives exclusively excitatory afferents from the cortex. Here we test the hypothesis that the dorsal striatum receives also GABAergic projections from the cortex. We addressed this fundamental question by taking advantage of optogenetics and directly examining the functional effects of cortical GABAergic inputs to spiny projection neurons (SPNs) of the mouse auditory and motor cortex. We found that the cortex, via corticostriatal somatostatin neurons (CS-SOM), has a direct inhibitory influence on the output of the striatum SPNs. Our results describe a corticostriatal long-range inhibitory circuit (CS-SOM inhibitory projections → striatal SPNs) underlying the control of spike timing/generation in SPNs and attributes a specific function to a genetically defined type of cortical interneuron in corticostriatal communication.DOI: http://dx.doi.org/10.7554/eLife.15890.001

Pyramidal cells in piriform cortex integrate sensory information from multiple olfactory bulb mitral and tufted (M/T) cells. However, whether M/T cells belonging to different olfactory bulb glomeruli converge onto individual cortical cells is unclear. Here we use calcium imaging in an olfactory bulb-cortex slice preparation to provide direct evidence that neurons in piriform cortex receive convergent synaptic input from different glomeruli. We show that the combined activity of distinct glomerular pathways recruits ensembles of pyramidal cells that are not activated by the individual pathways alone. This cooperative recruitment of cortical neurons only occurs over a narrow time window and is a feature intrinsic to the olfactory cortex that can be explained by the integration of converging, subthreshold synaptic input. Cooperative recruitment enhances the differences between cortical representations of partially overlapping input patterns and may contribute to the initial steps of olfactory discrimination.