A cortical circuit for gain control by behavioral state.

The brain's response to sensory input is strikingly modulated by behavioral state. Notably, the visual response of mouse primary visual cortex (V1) is enhanced by locomotion, a tractable and accessible example of a time-locked change in cortical state. The neural circuits that transmit behavioral state to sensory cortex to produce this modulation are unknown. In vivo calcium imaging of behaving animals revealed that locomotion activates vasoactive intestinal peptide (VIP)-positive neurons in mouse V1 independent of visual stimulation and largely through nicotinic inputs from basal forebrain. Optogenetic activation of VIP neurons increased V1 visual responses in stationary awake mice, artificially mimicking the effect of locomotion, and photolytic damage of VIP neurons abolished the enhancement of V1 responses by locomotion. These findings establish a cortical circuit for the enhancement of visual response by locomotion and provide a potential common circuit for the modulation of sensory processing by behavioral state.

Neonatal cerebral hypoxia-ischemia impairs plasticity in rat visual cortex.

Ocular dominance plasticity (ODP) following monocular deprivation (MD) is a model of activity-dependent neural plasticity that is restricted to an early critical period regulated by maturation of inhibition. Unique developmental plasticity mechanisms may improve outcomes following early brain injury. Our objective was to determine the effects of neonatal cerebral hypoxia-ischemia (HI) on ODP. The rationale extends from observations that neonatal HI results in death of subplate neurons, a transient population known to influence development of inhibition. In rodents subjected to neonatal HI and controls, maps of visual response were derived from optical imaging during the critical period for ODP and changes in the balance of eye-specific response following MD were measured. In controls, MD results in a shift of the ocular dominance index (ODI) from a baseline of 0.15 to -0.10 (p < 0.001). Neonatal HI with moderate cortical injury impairs this shift, ODI = 0.14 (p < 0.01). Plasticity was intact in animals with mild injury and in those exposed to hypoxia alone. Neonatal HI resulted in decreased parvalbumin expression in hemispheres receiving HI compared with hypoxia alone: 23.4 versus 35.0 cells/high-power field (p = 0.01), with no change in other markers of inhibitory or excitatory neurons. Despite abnormal inhibitory neuron phenotype, spontaneous activity of single units and development of orientation selective responses were intact following neonatal HI, while overall visual responses were reduced. Our data suggest that specific plasticity mechanisms are impaired following early brain injury and that the impairment is associated with altered inhibitory neuronal development and cortical activation.

Calcium-permeable AMPA receptors mediate glutamatergic signaling in neural precursor cells of the postnatal olfactory bulb.

Neural precursor cells (NPCs) in the mammalian olfactory bulb give rise to local inhibitory neurons that integrate into existing circuitry throughout adult life. However, the functional properties of neurotransmitter receptors expressed by NPCs are not well understood. In this study, we use patch-clamp recording and calcium imaging to explore the properties of glutamate receptors expressed by NPCs in the olfactory bulb subependymal layer. We find that calcium-permeable AMPA receptors (AMPARs) are the major receptor type underlying glutamatergic signaling in olfactory bulb NPCs. We also show that when transmitter uptake is reduced, glutamate spillover from distant nerve terminals in the olfactory bulb can activate nonsynaptic NPC AMPARs and generate increases in intracellular calcium. Together, these results suggest that Ca(2+) influx via AMPARs may contribute to calcium-dependent processes that govern NPC differentiation and maturation.

L-type calcium channels govern calcium signaling in migrating newborn neurons in the postnatal olfactory bulb.

Newborn inhibitory neurons migrate into existing neural circuitry in the olfactory bulb throughout the lifetime of adult mammals. While many factors contribute to the maturation of neural circuits, intracellular calcium is believed to play an important role in regulating cell migration and the development of neural systems. However, the factors underlying calcium signaling within newborn neurons in the postnatal olfactory bulb are not well understood. Here, we show that migrating, immature neurons in the olfactory bulb subependymal layer (SEL) undergo spontaneous and depolarization-evoked intracellular calcium transients mediated by high-voltage-activated L-type calcium channels. In contrast to migrating immature neurons in other brain regions, modulation of calcium transients in SEL cells does not alter their rate of migration.

Intraglomerular inhibition: signaling mechanisms of an olfactory microcircuit.

Microcircuits composed of principal neuron and interneuron dendrites have an important role in shaping the representation of sensory information in the olfactory bulb. Here we establish the physiological features governing synaptic signaling in dendrodendritic microcircuits of olfactory bulb glomeruli. We show that dendritic gamma-aminobutyric acid (GABA) release from periglomerular neurons mediates inhibition of principal tufted cells, retrograde inhibition of sensory input and lateral signaling onto neighboring periglomerular cells. We find that L-type dendritic Ca(2+) spikes in periglomerular cells underlie dendrodendritic transmission by depolarizing periglomerular dendrites and activating P/Q type channels that trigger GABA release. Ca(2+) spikes in periglomerular cells are evoked by powerful excitatory inputs from a single principal cell, and glutamate release from the dendrites of single principal neurons activates a large ensemble of periglomerular cells.