Patch-walking, a coordinated multi-pipette patch clamp for efficiently finding synaptic connections.

Significant technical challenges exist when measuring synaptic connections between neurons in living brain tissue. The patch clamping technique, when used to probe for synaptic connections, is manually laborious and time-consuming. To improve its efficiency, we pursued another approach: instead of retracting all patch clamping electrodes after each recording attempt, we cleaned just one of them and reused it to obtain another recording while maintaining the others.

Patch-walking: Coordinated multi-pipette patch clamp for efficiently finding synaptic connections.

Significant technical challenges exist when measuring synaptic connections between neurons in living brain tissue. The patch clamping technique, when used to probe for synaptic connections, is manually laborious and time-consuming. To improve its efficiency, we pursued another approach: instead of retracting all patch clamping electrodes after each recording attempt, we cleaned just one of them and reused it to obtain another recording while maintaining the others.

GABAergic synaptic scaling is triggered by changes in spiking activity rather than AMPA receptor activation.

Homeostatic plasticity represents a set of mechanisms that are thought to recover some aspect of neural function. One such mechanism called AMPAergic scaling was thought to be a likely candidate to homeostatically control spiking activity. However, recent findings have forced us to reconsider this idea as several studies suggest AMPAergic scaling is not directly triggered by changes in spiking.

Reward contingency gates selective cholinergic suppression of amygdala neurons.

Basal forebrain cholinergic neurons modulate how organisms process and respond to environmental stimuli through impacts on arousal, attention, and memory. It is unknown, however, whether basal forebrain cholinergic neurons are directly involved in conditioned behavior, independent of secondary roles in the processing of external stimuli. Using fluorescent imaging, we found that cholinergic neurons are active during behavioral responding for a reward - even prior to reward delivery and in the absence of discrete stimuli.

Investigation of the efficacy and safety of retinal inactivation as a treatment for amblyopia in cats.

Introduction: Deprivation of normal vision early in postnatal development elicits modifications of neural circuitry within the primary visual pathway that can cause a severe and intractable vision impairment (amblyopia). In cats, amblyopia is often modeled with monocular deprivation (MD), a procedure that involves temporarily closing the lids of one eye. Following long-term MD, brief inactivation of the dominant eye's retina can promote recovery from the anatomical and physiological effects of MD.

Correction of amblyopia in cats and mice after the critical period.

Monocular deprivation early in development causes amblyopia, a severe visual impairment. Prognosis is poor if therapy is initiated after an early critical period. However, clinical observations have shown that recovery from amblyopia can occur later in life when the non-deprived (fellow) eye is removed.

Divergent Synaptic Scaling of Miniature EPSCs following Activity Blockade in Dissociated Neuronal Cultures.

Neurons can respond to decreased network activity with a homeostatic increase in the amplitudes of miniature EPSCs (mEPSCs). The prevailing view is that mEPSC amplitudes are uniformly multiplied by a single factor, termed "synaptic scaling." Deviations from purely multiplicative scaling have been attributed to biological differences, or to a distortion imposed by a detection threshold limit.

Distinct Laminar Requirements for NMDA Receptors in Experience-Dependent Visual Cortical Plasticity.

Primary visual cortex (V1) is the locus of numerous forms of experience-dependent plasticity. Restricting visual stimulation to one eye at a time has revealed that many such forms of plasticity are eye-specific, indicating that synaptic modification occurs prior to binocular integration of thalamocortical inputs. A common feature of these forms of plasticity is the requirement for NMDA receptor (NMDAR) activation in V1.

Recovery from the anatomical effects of long-term monocular deprivation in cat lateral geniculate nucleus.

Monocular deprivation (MD) imposed early in postnatal life elicits profound structural and functional abnormalities throughout the primary visual pathway. The ability of MD to modify neurons within the visual system is restricted to a so-called critical period that, for cats, peaks at about one postnatal month and declines thereafter so that by about 3 months of age MD has little effect. Recovery from the consequences of MD likewise adheres to a critical period that ends by about 3 months of age, after which the effects of deprivation are thought to be permanent and without capacity for reversal.

Rapid recovery from the effects of early monocular deprivation is enabled by temporary inactivation of the retinas.

A half-century of research on the consequences of monocular deprivation (MD) in animals has revealed a great deal about the pathophysiology of amblyopia. MD initiates synaptic changes in the visual cortex that reduce acuity and binocular vision by causing neurons to lose responsiveness to the deprived eye. However, much less is known about how deprivation-induced synaptic modifications can be reversed to restore normal visual function.

Optogenetic feedback control of neural activity.

Optogenetic techniques enable precise excitation and inhibition of firing in specified neuronal populations and artifact-free recording of firing activity. Several studies have suggested that optical stimulation provides the precision and dynamic range requisite for closed-loop neuronal control, but no approach yet permits feedback control of neuronal firing. Here we present the 'optoclamp', a feedback control technology that provides continuous, real-time adjustments of bidirectional optical stimulation in order to lock spiking activity at specified targets over timescales ranging from seconds to days.

Upward synaptic scaling is dependent on neurotransmission rather than spiking.

Homeostatic plasticity encompasses a set of mechanisms that are thought to stabilize firing rates in neural circuits. The most widely studied form of homeostatic plasticity is upward synaptic scaling (upscaling), characterized by a multiplicative increase in the strength of excitatory synaptic inputs to a neuron as a compensatory response to chronic reductions in firing rate. While reduced spiking is thought to trigger upscaling, an alternative possibility is that reduced glutamatergic transmission generates this plasticity directly.

Delivery of continuously-varying stimuli using channelrhodopsin-2.

To study sensory processing, stimuli are delivered to the sensory organs of animals and evoked neural activity is recorded downstream. However, noise and uncontrolled modulatory input can interfere with repeatable delivery of sensory stimuli to higher brain regions. Here we show how channelrhodopsin-2 (ChR2) can be used to deliver continuous, subthreshold, time-varying currents to neurons at any point along the sensory-motor pathway.

Closed-Loop, Multichannel Experimentation Using the Open-Source NeuroRighter Electrophysiology Platform.

Single neuron feedback control techniques, such as voltage clamp and dynamic clamp, have enabled numerous advances in our understanding of ion channels, electrochemical signaling, and neural dynamics. Although commercially available multichannel recording and stimulation systems are commonly used for studying neural processing at the network level, they provide little native support for real-time feedback. We developed the open-source NeuroRighter multichannel electrophysiology hardware and software platform for closed-loop multichannel control with a focus on accessibility and low cost.