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1.
Cell Rep ; 33(3): 108272, 2020 10 20.
Article in English | MEDLINE | ID: mdl-33086072

ABSTRACT

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. Neuronal responses of V1 neurons are reduced in the disengaged state, but pupil diameter does not decrease, suggesting that animals' reduced level of arousal does not drive the transition to disengagement. Our findings indicate that satiation level alone does not have an instructive role in visually guided behavior and suggest that animals' behavior is governed by cost-benefit analysis that can override thirst signals.


Subject(s)
Motivation/physiology , Satiation/physiology , Animals , Behavior, Animal/physiology , Brain/physiology , Female , Hunger/physiology , Hypothalamus/physiology , Male , Mice , Mice, Inbred C57BL , Neurons/physiology , Reaction Time/physiology , Thirst/physiology , Visual Perception/physiology
2.
Neuron ; 99(6): 1289-1301.e2, 2018 09 19.
Article in English | MEDLINE | ID: mdl-30174117

ABSTRACT

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. These fluctuations are driven by correlated barrages of excitation followed closely by inhibition (∼5-ms lag). During visual stimulation, low-frequency activity is diminished, and coherent high-frequency oscillations appear, even for non-preferred stimuli. These oscillations are generated by alternating excitatory and inhibitory inputs at a similar lag. The temporal sequence of depolarization for pairs of neurons is conserved during both spontaneous- and visually-evoked activity, suggesting a stereotyped flow of activation that may function to produce temporally precise "windows of opportunity" for additional synaptic inputs.


Subject(s)
Membrane Potentials/physiology , Synapses/physiology , Visual Cortex/physiology , Wakefulness/physiology , Action Potentials/physiology , Animals , Mice , Neural Inhibition/physiology , Neurons/physiology , Photic Stimulation/methods
3.
Curr Biol ; 28(1): 114-120.e5, 2018 01 08.
Article in English | MEDLINE | ID: mdl-29276127

ABSTRACT

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.g., figure-ground segmentation and surround suppression) [2-5], and feedback has been demonstrated to sharpen orientation tuning of neurons in the primary visual cortex (V1) [6, 7]. However, the response characteristics of feedback neurons themselves and how feedback shapes V1 neurons' tuning for other features, such as spatial frequency (SF), remain largely unknown. Here, using a retrograde virus, targeted electrophysiological recordings, and optogenetic manipulations, we show that putatively feedback neurons in layer 5 (hereafter "L5 feedback") in higher visual areas, AL (anterolateral area) and PM (posteromedial area), display distinct visual properties in awake head-fixed mice. AL L5 feedback neurons prefer significantly lower SF (mean: 0.04 cycles per degree [cpd]) compared to PM L5 feedback neurons (0.15 cpd). Importantly, silencing AL L5 feedback reduced visual responses of V1 neurons preferring low SF (mean change in firing rate: -8.0%), whereas silencing PM L5 feedback suppressed responses of high-SF-preferring V1 neurons (-20.4%). These findings suggest that feedback connections from higher visual areas convey distinctly tuned visual inputs to V1 that serve to boost V1 neurons' responses to SF. Such like-to-like functional organization may represent an important feature of feedback pathways in sensory systems and in the nervous system in general.


Subject(s)
Action Potentials/physiology , Feedback , Neurons/physiology , Visual Cortex/physiology , Visual Perception/physiology , Animals , Female , Male , Mice
4.
J Neurosci ; 34(29): 9656-64, 2014 Jul 16.
Article in English | MEDLINE | ID: mdl-25031405

ABSTRACT

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. We found that the axons of L6 CT neurons densely ramified within layer 5a in both visual and somatosensory cortices of the mouse. Optogenetic activation of corticothalamic neurons generated large EPSPs in pyramidal neurons in layer 5a. In contrast, excitatory neurons in layer 4 exhibited weak excitation or disynaptic inhibition. Fast-spiking parvalbumin-positive cells in both layer 5a and layer 4 were also strongly activated by L6 CT neurons. The overall effect of L6 CT activation was to suppress layer 4 while eliciting action potentials in layer 5a pyramidal neurons. Together, our data indicate that L6 CT neurons strongly activate an output layer of the cortex.


Subject(s)
Cerebral Cortex/cytology , Neural Pathways/physiology , Neurons/physiology , Synapses/physiology , Thalamus/cytology , Animals , Cerebral Cortex/metabolism , Channelrhodopsins , Cholera Toxin/metabolism , Fluorescent Dyes/metabolism , Glutamate Decarboxylase/genetics , Glutamate Decarboxylase/metabolism , In Vitro Techniques , Integrases/genetics , Luminescent Proteins/genetics , Luminescent Proteins/metabolism , Membrane Potentials/drug effects , Membrane Potentials/genetics , Mice , Mice, Transgenic , Mutation/genetics , Neurons/classification , Photic Stimulation , Receptors, Neurotensin/genetics , Synaptophysin/genetics , Synaptophysin/metabolism , Thalamus/metabolism
5.
Neuron ; 83(2): 260-261, 2014 Jul 16.
Article in English | MEDLINE | ID: mdl-25033175

ABSTRACT

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.


Subject(s)
Brain Stem/physiology , Locomotion/physiology , Neurons/physiology , Visual Cortex/physiology , Animals
6.
Article in English | MEDLINE | ID: mdl-24734005

ABSTRACT

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. Here we review recent work studying the cell-type specificity of nicotinic signaling in the cortex, synaptic mechanisms mediating cholinergic transmission, and the potential functional role of nicotinic modulation.


Subject(s)
Cerebral Cortex/metabolism , Cholinergic Fibers/physiology , Nerve Net/metabolism , Neurons/metabolism , Receptors, Nicotinic/metabolism , Synaptic Transmission/physiology , Animals , Mice , Mice, Knockout
7.
Neuron ; 80(2): 350-7, 2013 Oct 16.
Article in English | MEDLINE | ID: mdl-24139040

ABSTRACT

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. We found that the signal-to-noise ratio for sensory responses was improved during locomotion by two mechanisms: (1) a decrease in membrane potential variability leading to a reduction in background firing rates and (2) an enhancement in the amplitude and reliability of visually evoked subthreshold responses mediated by an increase in total conductance and a depolarization of the stimulus-evoked reversal potential. Consistent with the enhanced signal-to-noise ratio for visual responses during locomotion, we demonstrate that performance is improved in a visual detection task during this behavioral state.


Subject(s)
Locomotion/physiology , Membrane Potentials/physiology , Visual Cortex/physiology , Wakefulness/physiology , Animals , Evoked Potentials, Visual/physiology , Mice , Neurons/physiology , Neurophysiological Monitoring , Photic Stimulation , Signal-To-Noise Ratio , Visual Perception/physiology
8.
Nat Rev Neurosci ; 14(3): 202-16, 2013 03.
Article in English | MEDLINE | ID: mdl-23385869

ABSTRACT

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. Moreover, we show that supervised classification models could automatically categorize interneurons in agreement with experts' assignments. These results demonstrate a practical and objective approach to the naming, characterization and classification of neurons based on community consensus.


Subject(s)
Algorithms , Cerebral Cortex/cytology , Interneurons/classification , Interneurons/cytology , Terminology as Topic , gamma-Aminobutyric Acid/metabolism , Animals , Bayes Theorem , Cerebral Cortex/metabolism , Cluster Analysis , Humans , Interneurons/metabolism
9.
J Neurosci ; 32(48): 17287-96, 2012 Nov 28.
Article in English | MEDLINE | ID: mdl-23197720

ABSTRACT

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. Here, we report that fast α7 receptor-mediated EPSCs in the mouse cortex are highly variable and insensitive to perturbations of acetylcholinesterase (AChE), while slow non-α7 receptor-mediated EPSCs are reliable and highly sensitive to AChE activity. Based on these data, we propose that the fast and slow nicotinic responses reflect differences in synaptic structure between cholinergic varicosities activating α7 and non-α7 classes of nicotinic receptors.


Subject(s)
Cerebral Cortex/physiology , Cholinergic Neurons/physiology , Excitatory Postsynaptic Potentials/physiology , Interneurons/physiology , Receptors, Nicotinic/metabolism , Acetylcholinesterase/pharmacology , Animals , Cerebral Cortex/cytology , Cerebral Cortex/drug effects , Cholinergic Neurons/cytology , Cholinergic Neurons/drug effects , Excitatory Postsynaptic Potentials/drug effects , Interneurons/cytology , Interneurons/drug effects , Mice , Mice, Transgenic
10.
J Neurosci ; 32(11): 3859-64, 2012 Mar 14.
Article in English | MEDLINE | ID: mdl-22423106

ABSTRACT

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.


Subject(s)
Action Potentials/physiology , Cerebral Cortex/physiology , Interneurons/physiology , Neural Inhibition/physiology , Receptors, Nicotinic/physiology , Synapses/physiology , Action Potentials/genetics , Animals , Axons/physiology , Cerebral Cortex/cytology , Cholinergic Neurons/physiology , Female , Interneurons/classification , Male , Mice , Mice, Transgenic , Reaction Time/genetics , Synapses/genetics , Time Factors , alpha7 Nicotinic Acetylcholine Receptor
12.
Neuron ; 71(2): 197-8, 2011 Jul 28.
Article in English | MEDLINE | ID: mdl-21791277

ABSTRACT

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.

13.
J Neurosci ; 31(30): 10767-75, 2011 Jul 27.
Article in English | MEDLINE | ID: mdl-21795529

ABSTRACT

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. Here, we investigated the developmental time course of synaptogenesis of FS cell in mouse visual cortex. In layer 5/6 (L5/6), we recorded from two or three FS and/or pyramidal (PYR) neurons to study the development of electrical and chemical synaptic interactions from postnatal day 3 (P3) to P18. We detected no evidence for functional connectivity for FS-FS or FS-PYR pairs at P3-P4. However, by P5-P6, we found that 20% of FS pairs were electrically coupled, and 24% of pairs were connected via GABAergic synapses; by P15-P18, 42% of FS pairs had established functional electrical synapses, and 47% of FS pairs were connected via GABAergic synapses. FS cell GABAergic inhibition of pyramidal cells showed a similar developmental time line, but no electrical coupling was detected for FS-PYR pairs. We found that synaptogenesis of electrical and GABAergic connections of FS cells takes place in the same period. Together, our results suggest that chemical and electrical connections among FS cells can contribute to patterned neocortical activity only by the end of the first postnatal week.


Subject(s)
Action Potentials/physiology , Electrical Synapses/physiology , Neocortex/cytology , Neural Inhibition/physiology , gamma-Aminobutyric Acid/metabolism , Action Potentials/genetics , Age Factors , Analysis of Variance , Animals , Animals, Newborn , Electrical Synapses/genetics , Glutamate Decarboxylase/genetics , Green Fluorescent Proteins/genetics , In Vitro Techniques , Inhibitory Postsynaptic Potentials/genetics , Inhibitory Postsynaptic Potentials/physiology , Mice , Mice, Transgenic , Neocortex/growth & development , Parvalbumins/metabolism , Pyramidal Cells/physiology , Signal Transduction/genetics , gamma-Aminobutyric Acid/genetics
14.
Curr Opin Neurobiol ; 19(4): 415-21, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19674891

ABSTRACT

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. These studies indicate that knowing the identity of both the presynaptic and postsynaptic cell type is key when analyzing neocortical circuits. Furthermore, identifying the circuit organization of particular cell types in the neocortex allows the recording and manipulation of each cell type's activity and the direct testing of its functional role in perception and behavior.


Subject(s)
Nerve Net/physiology , Neurons/physiology , Somatosensory Cortex/physiology , Animals , Neural Inhibition/physiology , Synapses/physiology , Synaptic Transmission/physiology
15.
Nature ; 457(7233): 1133-6, 2009 Feb 26.
Article in English | MEDLINE | ID: mdl-19151698

ABSTRACT

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. Here we show that the probability of synaptic connection depends on the functional identities of both the presynaptic and postsynaptic neurons. We first found that the frequency of monosynaptic connections among corticostriatal pyramidal neurons is significantly higher than among corticocortical or corticotectal pyramidal neurons. We then show that the probability of feed-forward connections from corticocortical neurons to corticotectal neurons is approximately three- to fourfold higher than the probability of monosynaptic connections among corticocortical or corticotectal cells. Moreover, we found that the average axodendritic overlap of the presynaptic and postsynaptic pyramidal neurons could not fully explain the differences in connection probability that we observed. The selective synaptic interactions we describe demonstrate that the organization of local networks of pyramidal cells reflects the long-range targets of both the presynaptic and postsynaptic neurons.


Subject(s)
Axons/metabolism , Pyramidal Cells/cytology , Animals , Mice , Mice, Inbred C57BL , Models, Neurological , Synapses/metabolism
16.
Nat Rev Neurosci ; 9(7): 557-68, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18568015

ABSTRACT

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. The problems inherent in this are particularly acute when studying cortical interneurons. To tackle this, we convened a representative group of researchers to agree on a set of terms to describe the anatomical, physiological and molecular features of GABAergic interneurons of the cerebral cortex. The resulting terminology might provide a stepping stone towards a future classification of these complex and heterogeneous cells. Consistent adoption will be important for the success of such an initiative, and we also encourage the active involvement of the broader scientific community in the dynamic evolution of this project.


Subject(s)
Cerebral Cortex/cytology , Interneurons , gamma-Aminobutyric Acid/metabolism , Action Potentials , Axons/ultrastructure , Cerebral Cortex/metabolism , Humans , Interneurons/classification , Interneurons/cytology , Interneurons/metabolism , Synapses/ultrastructure
17.
J Neurosci ; 28(10): 2633-41, 2008 Mar 05.
Article in English | MEDLINE | ID: mdl-18322106

ABSTRACT

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. Although recent studies have documented the effects of dopamine modulation of neocortical synaptic connections among excitatory cells and between excitatory and various inhibitory cells, the effects of dopamine receptor activation on GABAergic and electrical interactions among FS cells is not known. To resolve this, we recorded from pairs of FS cells in the infragranular layers of mouse neocortical slices and tested the effects of D(1)-like (D(1)/D(5)) receptor activation on these connections. We found that D(1)-like receptor activation modulated GABAergic but not electrical connections between them. A D(1)-like receptor agonist preserved the strength of electrical coupling but reduced the amplitude of IPSPs and IPSCs between FS cells. Our results suggest that D(1)-like receptor activation has synapse-specific effects within networks of FS cells, with potential implications for the generation of rhythmic activity in the neocortex.


Subject(s)
Action Potentials/physiology , Interneurons/physiology , Neocortex/physiology , Neural Conduction/physiology , Neural Inhibition/physiology , Receptors, Dopamine D1/metabolism , gamma-Aminobutyric Acid/physiology , Action Potentials/drug effects , Animals , Benzazepines/pharmacology , Cell Line , Electric Conductivity , Female , Inhibitory Postsynaptic Potentials/drug effects , Inhibitory Postsynaptic Potentials/physiology , Interneurons/drug effects , Male , Mice , Neocortex/drug effects , Neural Inhibition/drug effects , Receptors, Dopamine D1/agonists , Receptors, Dopamine D1/physiology
18.
Cereb Cortex ; 18(10): 2296-305, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18203691

ABSTRACT

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. CB(1)-IS synapses were characterized by a very high failure rate that contrasted with the high reliability of FS synapses. Furthermore, CB(1)-IS cells received excitatory inputs less frequently compared with FS cells and made significantly less frequent inhibitory contacts onto local pyramids. These distinct synaptic properties together with their characteristic irregular firing suggest that CB(1)-IS cells play different role in neocortical function than that of FS cells. Thus, whereas the synaptic properties of FS cells can allow them to impose high-frequency rhythmic oscillatory activity, those of CB(1)-IS cells may lead to disruption of fast rhythmic oscillations. Our results suggest that activity-dependent release of cannabinoids, by blocking CB(1)-IS synapses, may alter the role of inhibition in neocortical circuits.


Subject(s)
Neocortex/cytology , Neocortex/physiology , Receptor, Cannabinoid, CB1/physiology , Synapses/physiology , gamma-Aminobutyric Acid/physiology , Action Potentials/physiology , Animals , Cannabinoid Receptor Modulators/physiology , Gap Junctions/physiology , Green Fluorescent Proteins/genetics , Interneurons/physiology , Mice , Mice, Transgenic , Neural Inhibition/physiology , Neural Pathways/physiology , Neuronal Plasticity/physiology , Organ Culture Techniques , Pyramidal Cells/physiology
20.
Trends Neurosci ; 28(6): 304-9, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15927686

ABSTRACT

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. So far, at least five different neocortical networks defined by extensive and selective electrical coupling have been studied in the neocortex. These results could provide important clues to the understanding of functional cortical circuitry.


Subject(s)
Neocortex/cytology , Nerve Net/physiology , Neurons/physiology , Synapses/physiology , gamma-Aminobutyric Acid/metabolism , Animals , Gap Junctions/physiology , Neural Inhibition/physiology , Neural Networks, Computer , Neurons/classification , Synapses/classification
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