Olfactory bulb (OB) interneurons are continuously renewed throughout an animal's lifespan. Despite extensive investigation of this phenomenon, little is known about bulbar circuitry functioning and olfactory performances under conditions of ablated arrival of new neurons into the adult OB. To address this issue we performed morphological, electrophysiological, and behavioral analysis in mice with suppressed bulbar neurogenesis. Infusion of the antimitotic drug AraC to the lateral ventricle via 28 d osmotic minipumps abolished the arrival of newly born neurons into the adult OB without affecting the total number of granule cells. The number, dendritic arborization, and spine density of interneurons generated in adulthood, before pump installation, were also not affected by AraC treatment. As a result of ablated neurogenesis, mitral cells—the principal output neurons in the OB—receive fewer inhibitory synapses, display reduced frequency of spontaneous IPSCs, experience smaller dendrodendritic inhibition, and exhibit decreased synchronized activity. Consequently, short-term olfactory memory was drastically reduced in AraC-treated mice. In contrast, olfactory performances of AraC-treated animals were undistinguishable from those of control mice in other odor-associated tests, such as spontaneous odor discrimination and long-term odor-associative memory tasks. Altogether, our data highlight the importance of adult neurogenesis for the proper functioning of the OB network and imply that new bulbar interneurons are involved in some, but not all, odor-associated tasks.

Rebalancing strength between synapses: Activation of a neuronal pathway is often associated with inhibition of surrounding pathways. How locally coordinated synaptic plasticity occurs in vivo is not known, nor is its role in shaping neuronal responses. El-Boustani et al. paired optogenetic stimulation of single neurons with a visual input and were able to shift the neuron's receptive field toward the target location. Spines that expressed structural long-term potentiation had receptive fields overlapping the target stimulus but were surrounded by spines that expressed receptive fields away from the target. Science , this issue p. 1349

Significance: Understanding neurophysiological correlates of neurodevelopmental disorders is one of the pressing challenges of neuroscience. By analyzing a mouse model of Rett syndrome (RTT), we show that cortical pyramidal neurons in methyl-CpG binding protein 2 (MeCP2) mutant mice have reduced excitatory as well as inhibitory synaptic drive. Thus, neuronal response reliability and selectivity, features that arise from excitatory/inhibitory processing circuits within cortex, are reduced. MeCP2 deletion crucially regulates inhibition via two complementary mechanisms: reducing responses of parvalbumin-expressing (PV ⁺ ) inhibitory neurons and altering the polarity of GABAergic inhibition in pyramidal neurons. Treating mutant mice with recombinant human insulin-like growth factor-1 (rhIGF1) restores GABAergic polarity along with PV ⁺ and pyramidal neuron responses, thus providing a mechanistic basis of action of rhIGF1 in RTT.

Sensorimotor behaviors require processing of behaviorally relevant sensory cues and the ability to select appropriate responses from a vast behavioral repertoire. Modulation by the prefrontal cortex (PFC) is thought to be key for both processes, but the precise role of specific circuits remains unclear. We examined the sensorimotor function of anatomically distinct outputs from a subdivision of the mouse PFC, the anterior cingulate cortex (ACC). Using a visually guided two-choice behavioral paradigm with multiple cue-response mappings, we dissociated the sensory and motor response components of sensorimotor control. Projection-specific two-photon calcium imaging and optogenetic manipulations show that ACC outputs to the superior colliculus, a key midbrain structure for response selection, principally coordinate specific motor responses. Importantly, ACC outputs exert control by reducing the innate response bias of the superior colliculus. In contrast, ACC outputs to the visual cortex facilitate sensory processing of visual cues. Our results ascribe motor and sensory roles to ACC projections to the superior colliculus and the visual cortex and demonstrate for the first time a circuit motif for PFC function wherein anatomically non-overlapping output pathways coordinate complementary but distinct aspects of visual sensorimotor behavior.