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Neurons typically receive synaptic input in their dendritic arbor, integrate inputs in their soma, and send output action potentials through their axon, following Cajal’s law of dynamic polarization. Two notable exceptions are retinal amacrine cells and olfactory granule cells (GCs), which flout Cajal’s edict by providing synaptic output from the same dendrites that collect synaptic input. Amacrine cells, a diverse cell class comprising >60 subtypes, employ various dendritic input/output strategies, but A17 amacrine cells (A17s) in particular share further interesting functional characteristics with GCs: both receive excitatory synaptic input from neurons in the primary glutamatergic pathway and return immediate, reciprocal feedback via GABAergic inhibitory synapses to the same synaptic terminals that provided input. Both neurons thereby process signals locally within their dendrites, shaping many parallels, signaling pathways independently. The similarities between A17s and GCs cast into relief striking differences that may indicate distinct processing roles within their respective circuits: First, they employ partially dissimilar molecular mechanisms to transform excitatory input into inhibitory output; second, GCs fire action potentials, whereas A17s do not. Third, GC signals may be influenced by cortical feedback, whereas the mammalian retina receives no such retrograde input. Finally, A17s constitute just one subtype within a diverse class that is specialized in a particular task, whereas the more homogeneous GCs may play more diverse signaling roles via multiple processing modes. Here, we review these analogies and distinctions between A17 amacrine cells and granule cells, hoping to gain further insight into the operating principles of these two sensory circuits.

Neurons typically receive synaptic input in their dendritic arbor, integrate inputs in their soma, and send output action potentials through their axon, following Cajal's law of dynamic polarization. Two notable exceptions are retinal amacrine cells and olfactory granule cells (GCs), which flout Cajal's edict by providing synaptic output from the same dendrites that collect synaptic input. Amacrine cells, a diverse cell class comprising >60 subtypes, employ various dendritic input/output strategies, but A17 amacrine cells (A17s) in particular share further interesting functional characteristics with GCs: both receive excitatory synaptic input from neurons in the primary glutamatergic pathway and return immediate, reciprocal feedback via GABAergic inhibitory synapses to the same synaptic terminals that provided input. Both neurons thereby process signals locally within their dendrites, shaping many parallels, signaling pathways independently. The similarities between A17s and GCs cast into relief striking differences that may indicate distinct processing roles within their respective circuits: First, they employ partially dissimilar molecular mechanisms to transform excitatory input into inhibitory output; second, GCs fire action potentials, whereas A17s do not. Third, GC signals may be influenced by cortical feedback, whereas the mammalian retina receives no such retrograde input. Finally, A17s constitute just one subtype within a diverse class that is specialized in a particular task, whereas the more homogeneous GCs may play more diverse signaling roles via multiple processing modes. Here, we review these analogies and distinctions between A17 amacrine cells and granule cells, hoping to gain further insight into the operating principles of these two sensory circuits. [ABSTRACT FROM AUTHOR]

It is well described that A1 adenosine receptors inhibit synaptic transmission at excitatory synapses in the brain, but the effect of adenosine on reciprocal synapses has not been studied so far. In the olfactory bulb, the majority of synapses are reciprocal dendro-dendritic synapses mediating recurrent inhibition. We studied the effect of A1 receptor activation on recurrent dendro-dendritic inhibition in mitral cells using whole-cell patch-clamp recordings. Adenosine reduced dendro-dendritic inhibition in wild-type, but not in A1 receptor knock-out mice. Both NMDA receptor-mediated and AMPA receptor-mediated dendro-dendritic inhibition were attenuated by adenosine, indicating that reciprocal synapses between mitral cells and granule cells as well as parvalbumin interneurons were targeted by A1 receptors. Adenosine reduced glutamatergic self-excitation and inhibited N-type and P/Q-type calcium currents, but not L-type calcium currents in mitral cells. Attenuated glutamate release, due to A1 receptor-mediated calcium channel inhibition, resulted in impaired dendro-dendritic inhibition. In behavioral tests we tested the ability of wild-type and A1 receptor knock-out mice to find a hidden piece of food. Knock-out mice were significantly faster in locating the food. Our results indicate that A1 adenosine receptors attenuates dendro-dendritic reciprocal inhibition and suggest that they affect odor information processing.

It is well described that A1 adenosine receptors inhibit synaptic transmission at excitatory synapses in the brain, but the effect of adenosine on reciprocal synapses has not been studied so far. In the olfactory bulb, the majority of synapses are reciprocal dendro-dendritic synapses mediating recurrent inhibition. We studied the effect of A1 receptor activation on recurrent dendro-dendritic inhibition in mitral cells using wholecell patch-clamp recordings. Adenosine reduced dendro-dendritic inhibition in wild-type, but not in A1 receptor knock-out mice. Both NMDA receptor-mediated and AMPA receptor-mediated dendro-dendritic inhibition were attenuated by adenosine, indicating that reciprocal synapses between mitral cells and granule cells as well as parvalbumin interneurons were targeted by A1 receptors. Adenosine reduced glutamatergic selfexcitation and inhibited N-type and P/Q-type calcium currents, but not L-type calcium currents in mitral cells. Attenuated glutamate release, due to A1 receptor-mediated calcium channel inhibition, resulted in impaired dendro-dendritic inhibition. In behavioral tests we tested the ability of wild-type and A1 receptor knock-out mice to find a hidden piece of food. Knock-out mice were significantly faster in locating the food. Our results indicate that A1 adenosine receptors attenuates dendro-dendritic reciprocal inhibition and suggest that they affect odor information processing. [ABSTRACT FROM AUTHOR]