Dendritic spines compartmentalize synaptically-evoked biochemical signals. The authors show that electrical compartmentalization provided by a spine endows the associated synapse with additional modes of calcium signaling by shaping the kinetics of synaptic calcium currents.

Acetylcholine release and activation of muscarinic cholinergic receptors (mAChRs) enhance synaptic plasticity in vitro and cognition and memory in vivo. Within the hippocampus, mAChRs enhance NMDA-type glutamate receptor-dependent forms of long-term potentiation. Here, we use calcium (Ca) imaging combined with 2-photon laser glutamate uncaging at apical spines of CA1 pyramidal neurons to examine post-synaptic mechanisms of muscarinic modulation of glutamatergic transmission. Uncaging-evoked excitatory post-synaptic potentials and Ca transients are increased by muscarinic stimulation; however, this is not due to direct modulation of glutamate receptors. Instead, mAChRs modulate a negative feedback loop in spines that normally suppresses synaptic signals. mAChR activation reduces the Ca sensitivity of small conductance Ca-activated potassium (SK) channels that are found in the spine, resulting in increased synaptic potentials and Ca transients. These effects are mediated by M1-type muscarinic receptors and occur in a casein kinase-2 dependent manner. Thus, muscarinic modulation regulates synaptic transmission by tuning the activity of non-glutamatergic post-synaptic ion channels.

Sensory information in the visual, auditory and somatosensory systems is organized topographically, with key sensory features ordered in space across neural sheets. Despite the existence of a spatially stereotyped map of odor identity within the olfactory bulb, it is unclear whether the higher olfactory cortex uses topography to organize information about smells. Here, we review recent work on the anatomy, microcircuitry and neuromodulation of two higher-order olfactory areas: the piriform cortex and the olfactory tubercle. The piriform is an archicortical region with an extensive local associational network that constructs representations of odor identity. The olfactory tubercle is an extension of the ventral striatum that may use reward-based learning rules to encode odor valence. We argue that in contrast to brain circuits for other sensory modalities, both the piriform and the olfactory tubercle largely discard any topography present in the bulb and instead use distributive afferent connectivity, local learning rules and input from neuromodulatory centers to build representations of behaviorally relevant properties of olfactory stimuli.