Optogenetics in the behaving rat: integration of diverse new technologies in a vital animal model

Zalocusky, Kelly A.; Deisseroth, Karl

doi:10.2478/optog-2013-0001

Cited by 23 publications

(9 citation statements)

References 207 publications

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“…While there are a number of methods for inactivating brain regions including physical lesions [1], pharmacological inactivation [2], optogenetics [3] and chemogenetics [4], inactivation by cooling [5] is particularly advantageous for manipulating large areas of tissue that may be intractable when using genetic tools or optical stimulation/suppression [6]. Furthermore unlike physical lesions and slow-release implantable drugs, the effects of cooling are acute and reversible [5], limiting the potential for other brain regions to compensate for the loss of neural function and allowing within-subject comparison of interleaved control and inactivation sessions [7].…”

Section: Introductionmentioning

confidence: 99%

Acute Inactivation of Primary Auditory Cortex Causes a Sound Localisation Deficit in Ferrets

et al. 2017

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The objective of this study was to demonstrate the efficacy of acute inactivation of brain areas by cooling in the behaving ferret and to demonstrate that cooling auditory cortex produced a localisation deficit that was specific to auditory stimuli. The effect of cooling on neural activity was measured in anesthetized ferret cortex. The behavioural effect of cooling was determined in a benchmark sound localisation task in which inactivation of primary auditory cortex (A1) is known to impair performance. Cooling strongly suppressed the spontaneous and stimulus-evoked firing rates of cortical neurons when the cooling loop was held at temperatures below 10°C, and this suppression was reversed when the cortical temperature recovered. Cooling of ferret auditory cortex during behavioural testing impaired sound localisation performance, with unilateral cooling producing selective deficits in the hemifield contralateral to cooling, and bilateral cooling producing deficits on both sides of space. The deficit in sound localisation induced by inactivation of A1 was not caused by motivational or locomotor changes since inactivation of A1 did not affect localisation of visual stimuli in the same context.

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Section: Introductionmentioning

confidence: 99%

Acute Inactivation of Primary Auditory Cortex Causes a Sound Localisation Deficit in Ferrets

et al. 2017

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“…Specification of defined neural pathways for optogenetic perturbation has been achieved in a number of ways (reviewed in Deisseroth, 2014; Packer et al, 2013; Zalocusky and Deisseroth, 2013). One approach (called projection targeting) relies on optogenetic actuator expression in an upstream neuronal population defined by focal virus injection; a subset of these neurons (defined by having efferent connections to a spatially-separated downstream brain area) is then selected by restricting light delivery to excite or inhibit the axons of this neuronal subpopulation in the target brain region (or, more generally, in a location that distinguishes the pathway of interest) in vivo during behavior (Gradinaru et al, 2009; Tye et al, 2011; Stuber et al, 2011).…”

Section: Observing and Controlling Population And Projection Dynamicsmentioning

confidence: 99%

Closed-Loop and Activity-Guided Optogenetic Control

Grosenick

Marshel

Deisseroth

2015

Neuron

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346

322

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Advances in optical manipulation and observation of neural activity have set the stage for widespread implementation of closed-loop and activity-guided optical control of neural circuit dynamics. Closing the loop optogenetically (i.e., basing optogenetic stimulation on simultaneously observed dynamics in a principled way) is a powerful strategy for causal investigation of neural circuitry. In particular, observing and feeding back the effects of circuit interventions on physiologically relevant timescales is valuable for directly testing whether inferred models of dynamics, connectivity, and causation are accurate in vivo. Here we highlight technical and theoretical foundations as well as recent advances and opportunities in this area, and we review in detail the known caveats and limitations of optogenetic experimentation in the context of addressing these challenges with closed-loop optogenetic control in behaving animals.

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“…Inhibition of a subset of myelinated neurons using the powerful molecular tools available to control neuronal activity would permit probing their role in normal and neuropathic conditions [2,5,11,35,54,57]. Optically active channels and pumps are one such tool and hold promise for therapeutic application and interrogation of cellular systems [3,8,11,19,29,36].…”

Section: 0 Introductionmentioning

confidence: 99%

Fast-conducting mechanoreceptors contribute to withdrawal behavior in normal and nerve injured rats

Boada

Martin

Peters

et al. 2014

Pain

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Fast conducting myelinated high threshold mechanoreceptors (AHTMR) are largely thought to transmit acute nociception from the periphery. However, their roles in normal withdrawal and in nerve injury induced hyperalgesia are less well accepted. Modulation of this subpopulation of peripheral neurons would help define their roles in withdrawal behaviors. The optically active proton pump, ArchT, was placed in an AAV8 viral vector with the CAG promoter and was administered by intrathecal injection resulting in expression in myelinated neurons. Optical inhibition of peripheral neurons at the soma and transcutaneously was possible in the neurons expressing ArchT, but not in neurons from control animals. Receptive field characteristics and electrophysiology determined that inhibition was neuronal subtype specific with only AHTMR neurons being inhibited. One week following nerve injury the AHTMR are hyperexcitable, but can still be inhibited at the soma and transcutaneously. Withdrawal thresholds to mechanical stimuli in normal and in hyperalgesic nerve injured animals were also increased by transcutaneous light to the affected hindpaw. This suggests that AHTMR neurons play a role not only in threshold related withdrawal behavior in the normal animal, but also in sensitized states after nerve injury. This is the first time this subpopulation of neurons has been reversibly modulated to test their contribution to withdrawal related behaviors before and after nerve injury. This technique may prove useful to define the role of selective neuronal populations in different pain states.

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Optogenetics in the behaving rat: integration of diverse new technologies in a vital animal model

Cited by 23 publications

References 207 publications

Acute Inactivation of Primary Auditory Cortex Causes a Sound Localisation Deficit in Ferrets

Acute Inactivation of Primary Auditory Cortex Causes a Sound Localisation Deficit in Ferrets

Closed-Loop and Activity-Guided Optogenetic Control

Fast-conducting mechanoreceptors contribute to withdrawal behavior in normal and nerve injured rats

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