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Papers by Sergio Ortiz Arroyo

Research paper thumbnail of Nicotinic modulation of cortical circuits

Frontiers in Neural Circuits, 2014

The ascending cholinergic neuromodulatory system sends projections throughout cortex and has been... more 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.

Research paper thumbnail of Controlling Brain States

Neuron, 2014

Neurons in mouse V1 increase their response to visual stimulation during locomotion. In this issu... more 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.

Research paper thumbnail of Mechanisms Generating Dual-Component Nicotinic EPSCs in Cortical Interneurons

Journal of Neuroscience, 2012

Activation of cortical nicotinic receptors by cholinergic axons from the basal forebrain (BF) sig... more 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 ␣7 and a slow non-␣7 receptor-dependent response in cortical interneurons. However, the synaptic mechanisms that underlie this dual-component nicotinic response remain unclear. Here, we report that fast ␣7 receptormediated EPSCs in the mouse cortex are highly variable and insensitive to perturbations of acetylcholinesterase (AChE), while slow non-␣7 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 ␣7 and non-␣7 classes of nicotinic receptors.

Research paper thumbnail of Prolonged Disynaptic Inhibition in the Cortex Mediated by Slow, Non- 7 Nicotinic Excitation of a Specific Subset of Cortical Interneurons

Journal of Neuroscience, 2012

Cholinergic activation of nicotinic receptors in the cortex plays a critical role in arousal, att... more 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-␣7 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.

Research paper thumbnail of Subthreshold Mechanisms Underlying State-Dependent Modulation of Visual Responses

Neuron, 2013

The processing of sensory information varies widely across behavioral states. However, little is ... more 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 stimulusevoked 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.

Research paper thumbnail of Nicotinic modulation of cortical circuits

Frontiers in Neural Circuits, 2014

The ascending cholinergic neuromodulatory system sends projections throughout cortex and has been... more 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.

Research paper thumbnail of Controlling Brain States

Neuron, 2014

Neurons in mouse V1 increase their response to visual stimulation during locomotion. In this issu... more 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.

Research paper thumbnail of Mechanisms Generating Dual-Component Nicotinic EPSCs in Cortical Interneurons

Journal of Neuroscience, 2012

Activation of cortical nicotinic receptors by cholinergic axons from the basal forebrain (BF) sig... more 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 ␣7 and a slow non-␣7 receptor-dependent response in cortical interneurons. However, the synaptic mechanisms that underlie this dual-component nicotinic response remain unclear. Here, we report that fast ␣7 receptormediated EPSCs in the mouse cortex are highly variable and insensitive to perturbations of acetylcholinesterase (AChE), while slow non-␣7 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 ␣7 and non-␣7 classes of nicotinic receptors.

Research paper thumbnail of Prolonged Disynaptic Inhibition in the Cortex Mediated by Slow, Non- 7 Nicotinic Excitation of a Specific Subset of Cortical Interneurons

Journal of Neuroscience, 2012

Cholinergic activation of nicotinic receptors in the cortex plays a critical role in arousal, att... more 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-␣7 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.

Research paper thumbnail of Subthreshold Mechanisms Underlying State-Dependent Modulation of Visual Responses

Neuron, 2013

The processing of sensory information varies widely across behavioral states. However, little is ... more 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 stimulusevoked 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.