Motivation and Engagement during Visually Guided Behavior.

Animal behavior is motivated by internal drives, such as thirst and hunger, generated in hypothalamic neurons that project widely to many brain areas. We find that water-restricted mice maintain stable, high-level contrast sensitivity and brief reaction time while performing a visual task, but then abruptly stop and become disengaged. Mice consume a significant amount of water when freely provided in their home cage immediately after the task, indicating that disengagement does not reflect cessation of thirst.

Correlation of Synaptic Inputs in the Visual Cortex of Awake, Behaving Mice.

The subthreshold mechanisms that underlie neuronal correlations in awake animals are poorly understood. Here, we perform dual whole-cell recordings in the visual cortex (V1) of awake mice to investigate membrane potential (Vm) correlations between upper-layer sensory neurons. We find that the membrane potentials of neighboring neurons display large, correlated fluctuations during quiet wakefulness, including pairs of cells with disparate tuning properties.

Feature-Specific Organization of Feedback Pathways in Mouse Visual Cortex.

Higher and lower cortical areas in the visual hierarchy are reciprocally connected [1]. Although much is known about how feedforward pathways shape receptive field properties of visual neurons, relatively little is known about the role of feedback pathways in visual processing. Feedback pathways are thought to carry top-down signals, including information about context (e.

Controlling brain states.

Neurons in mouse V1 increase their response to visual stimulation during locomotion. In this issue of Neuron, Lee et al. (2014) show that subthreshold optogenetic stimulation of a brainstem locomotion area can mimic the effect of locomotion on sensory processing.

Layer 6 corticothalamic neurons activate a cortical output layer, layer 5a.

Layer 6 corticothalamic neurons are thought to modulate incoming sensory information via their intracortical axons targeting the major thalamorecipient layer of the neocortex, layer 4, and via their long-range feedback projections to primary sensory thalamic nuclei. However, anatomical reconstructions of individual layer 6 corticothalamic (L6 CT) neurons include examples with axonal processes ramifying within layer 5, and the relative input of the overall population of L6 CT neurons to layers 4 and 5 is not well understood. We compared the synaptic impact of L6 CT cells on neurons in layers 4 and 5.

Nicotinic modulation of cortical circuits.

The ascending cholinergic neuromodulatory system sends projections throughout cortex and has been shown to play an important role in a number of cognitive functions including arousal, working memory, and attention. However, despite a wealth of behavioral and anatomical data, understanding how cholinergic synapses modulate cortical function has been limited by the inability to selectively activate cholinergic axons. Now, with the development of optogenetic tools and cell-type specific Cre-driver mouse lines, it has become possible to stimulate cholinergic axons from the basal forebrain (BF) and probe cholinergic synapses in the cortex for the first time.

Subthreshold mechanisms underlying state-dependent modulation of visual responses.

The processing of sensory information varies widely across behavioral states. However, little is known about how behavioral states modulate the intracellular activity of cortical neurons to effect changes in sensory responses. Here, we performed whole-cell recordings from neurons in upper-layer primary visual cortex of awake mice during locomotion and quiet wakefulness.

New insights into the classification and nomenclature of cortical GABAergic interneurons.

A systematic classification and accepted nomenclature of neuron types is much needed but is currently lacking. This article describes a possible taxonomical solution for classifying GABAergic interneurons of the cerebral cortex based on a novel, web-based interactive system that allows experts to classify neurons with pre-determined criteria. Using Bayesian analysis and clustering algorithms on the resulting data, we investigated the suitability of several anatomical terms and neuron names for cortical GABAergic interneurons.

Mechanisms generating dual-component nicotinic EPSCs in cortical interneurons.

Activation of cortical nicotinic receptors by cholinergic axons from the basal forebrain (BF) significantly impacts cortical function, and the loss of nicotinic receptors is a hallmark of aging and neurodegenerative disease. We have previously shown that stimulation of BF axons generates a fast α7 and a slow non-α7 receptor-dependent response in cortical interneurons. However, the synaptic mechanisms that underlie this dual-component nicotinic response remain unclear.

Prolonged disynaptic inhibition in the cortex mediated by slow, non-α7 nicotinic excitation of a specific subset of cortical interneurons.

Cholinergic activation of nicotinic receptors in the cortex plays a critical role in arousal, attention, and learning. Here we demonstrate that cholinergic axons from the basal forebrain of mice excite a specific subset of cortical interneurons via a remarkably slow, non-α7 nicotinic receptor-mediated conductance. In turn, these inhibitory cells generate a delayed and prolonged wave of disynaptic inhibition in neighboring cortical neurons, altering the spatiotemporal pattern of inhibition in cortical circuits.

Synaptogenesis of electrical and GABAergic synapses of fast-spiking inhibitory neurons in the neocortex.

Parvalbumin-expressing fast-spiking (FS) cells are interconnected via GABAergic and electrical synapses and represent a major class of inhibitory interneurons in the neocortex. Synaptic connections among FS cells are critical for regulating network oscillations in the mature neocortex. However, it is unclear whether synaptic connections among FS interneurons also play a central role in the generation of patterned neuronal activity in the immature brain, which is thought to underlie the formation of neocortical circuits.

Noradrenaline enhances signal-to-noise ratio of inhibitory inputs in the dorsal cochlear nucleus.

What are the mechanisms that enhance the response to behaviorally relevant external stimuli? In this issue of Neuron, Kuo and Trussell show that in the dorsal cochlear nucleus, noradrenaline functions to simultaneously reduce spontaneous inhibitory inputs while increasing evoked inhibition.

Cell-type identity: a key to unlocking the function of neocortical circuits.

A central tenet of neuroscience is that the precise patterns of connectivity among neurons in a given brain area underlie its function. However, assigning any aspect of perception or behavior to the wiring of local circuits has been challenging. Here, we review recent work in sensory neocortex that demonstrates the power of identifying specific cell types when investigating the functional organization of brain circuits.

Intracortical circuits of pyramidal neurons reflect their long-range axonal targets.

Cortical columns generate separate streams of information that are distributed to numerous cortical and subcortical brain regions. We asked whether local intracortical circuits reflect these different processing streams by testing whether the intracortical connectivity among pyramidal neurons reflects their long-range axonal targets. We recorded simultaneously from up to four retrogradely labelled pyramidal neurons that projected to the superior colliculus, the contralateral striatum or the contralateral cortex to assess their synaptic connectivity.

Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex.

Neuroscience produces a vast amount of data from an enormous diversity of neurons. A neuronal classification system is essential to organize such data and the knowledge that is derived from them. Classification depends on the unequivocal identification of the features that distinguish one type of neuron from another.

D1-like dopamine receptor activation modulates GABAergic inhibition but not electrical coupling between neocortical fast-spiking interneurons.

Dopamine, acting through D(1) receptors, is thought to play an important role in cognitive functions of the frontal cortex such as working memory. D(1) receptors are widely expressed in fast-spiking (FS) interneurons, a prominent class of inhibitory cells that exert a powerful control of neuronal firing through proximal synapses on their postsynaptic targets. FS cells are extensively mutually interconnected by both GABA(A) receptor-mediated synapses and gap junction-mediated electrical synapses, and networks of FS cells play a crucial role in the generation of rhythmic synchronous activity.

Cannabinoid sensitivity and synaptic properties of 2 GABAergic networks in the neocortex.

Distinct networks of gamma-aminobutyric acidergic interneurons connected by electrical synapses can promote different patterns of activity in the neocortex. Cannabinoids affect memory and cognition by powerfully modulating a subset of inhibitory synapses; however, very little is known about the synaptic properties of the cannabinoid receptor-expressing neurons (CB(1)-positive irregular spiking [CB(1)-IS]) in the neocortex. Using paired recordings in neocortical slices, we 1st report here that synapses of CB(1)-IS cells, but not synapses of fast-spiking (FS) cells, are suppressed by release of endocannabinoids from pyramidal neurons.

Electrical synapses define networks of neocortical GABAergic neurons.

Recent work using paired recording has provided a direct demonstration of functional electrical synapses between neocortical neurons of both juvenile and adult animals. Electrical synapses have been found among GABAergic interneurons but not pyramidal cells. Interestingly, necortical electrical synapses almost exclusively connect GABAergic neurons belonging to the same class.

Background synaptic conductance and precision of EPSP-spike coupling at pyramidal cells.

The temporal precision of converting excitatory postsynaptic potentials (EPSPs) into spikes at pyramidal cells is critical for the coding of information in the cortex. Several in vitro studies have shown that voltage-dependent conductances in pyramidal cells can prolong the EPSP time course resulting in an imprecise EPSP-spike coupling. We have used dynamic-clamp techniques to mimic the in vivo background synaptic conductance in cortical slices and investigated how the ongoing synaptic activity may affect the EPSP time course near threshold and the EPSP spike coupling.

Electrical coupling among irregular-spiking GABAergic interneurons expressing cannabinoid receptors.

Anatomical studies have shown that the G-protein-coupled cannabinoid receptor-1 (CB1) is selectively expressed in a subset of GABAergic interneurons. It has been proposed that these cells regulate rhythmic activity and play a key role mediating the cognitive actions of marijuana and endogenous cannabinoids. However, the physiology, anatomy, and synaptic connectivity of neocortical CB1-expressing interneurons remain poorly studied.

Synaptic interactions of late-spiking neocortical neurons in layer 1.

Layer 1 of the neocortex is an important zone in which synaptic integration of inputs originating from a variety of cerebral regions is thought to take place. Layer 1 does not contain pyramidal cells, and several histochemical studies have suggested that most layer 1 neurons are GABAergic. However, although layer 1 neurons could be an important source of inhibition in this layer, the synaptic action of these neurons and the identity of their postsynaptic targets are unknown.

Electrical and chemical synapses among parvalbumin fast-spiking GABAergic interneurons in adult mouse neocortex.

Networks of gamma-aminobutyric acid (GABA)ergic interneurons connected via electrical and chemical synapses are thought to play an important role in detecting and promoting synchronous activity in the cerebral cortex. Although the properties of electrical and chemical synaptic interactions among inhibitory interneurons are critical for their function as a network, they have only been studied systematically in juvenile animals. Here, we have used transgenic mice expressing the enhanced green fluorescent protein in cells containing parvalbumin (PV) to study the synaptic connectivity among fast-spiking (FS) cells in slices from adult animals (2-7 months old).

Spike transmission and synchrony detection in networks of GABAergic interneurons.

The temporal pattern and relative timing of action potentials among neocortical neurons may carry important information. However, how cortical circuits detect or generate coherent activity remains unclear. Using paired recordings in rat neocortical slices, we found that the firing of fast-spiking cells can reflect the spiking pattern of single-axon pyramidal inputs.