Although neuronal excitability is well understood and accurately modeled over timescales of up to hundreds of milliseconds, it is currently unclear whether extrapolating from this limited duration to longer behaviorally relevant timescales is appropriate. Here we used an extracellular recording and stimulation paradigm that extends the duration of single-neuron electrophysiological experiments, exposing the dynamics of excitability in individual cultured cortical neurons over timescales hitherto inaccessible. We show that the long-term neuronal excitability dynamics is unstable and dominated by critical fluctuations, intermittency, scale-invariant rate statistics, and long memory. These intrinsic dynamics bound the firing rate over extended timescales, contrasting observed short-term neuronal response to stimulation onset. Furthermore, the activity of a neuron over extended timescales shows transitions between quasi-stable modes, each characterized by a typical response pattern. Like in the case of rate statistics, the short-term onset response pattern that often serves to functionally define a given neuron is not indicative of its long-term ongoing response. These observations question the validity of describing neuronal excitability based on temporally restricted electrophysiological data, calling for in-depth exploration of activity over wider temporal scales. Such extended experiments will probably entail a different kind of neuronal models, accounting for the unbounded range, from milliseconds up.

To attribute spatial meaning to sensory information, the state of the sensory organ must be represented in the nervous system. In the rodent's vibrissal system, the whisking-cycle phase has been identified as a key coordinate, and phase-based representation of touch has been reported in the somatosensory cortex. Where and how phase is extracted in the ascending afferent pathways remains unknown. Using a closed-loop interface in anesthetized rats, we found that whisking phase is already encoded in a frequency- and amplitude-invariant manner by primary vibrissal afferents. We found that, for naturally constrained whisking dynamics, such invariant phase coding could be obtained by tuning each receptor to a restricted kinematic subspace. Invariant phase coding was preserved in the brainstem, where paralemniscal neurons filtered out the slowly evolving offset, whereas lemniscal neurons preserved it. These results demonstrate accurate, perceptually relevant, mechanically based processing at the sensor level.

Learning the spatial organization of the environment is essential for most animals’ survival. This requires the animal to derive allocentric spatial information from egocentric sensory and motor experience. The neural mechanisms underlying this transformation are mostly unknown. We addressed this problem in electric fish, which can precisely navigate in complete darkness and whose brain circuitry is relatively simple. We conducted the first neural recordings in the preglomerular complex, the thalamic region exclusively connecting the optic tectum with the spatial learning circuits in the dorsolateral pallium. While tectal topographic information was mostly eliminated in preglomerular neurons, the time-intervals between object encounters were precisely encoded. We show that this reliable temporal information, combined with a speed signal, can permit accurate estimation of the distance between encounters, a necessary component of path-integration that enables computing allocentric spatial relations. Our results suggest that similar mechanisms are involved in sequential spatial learning in all vertebrates.

Responses of individual neurons to ongoing input are highly variable, reflecting complex threshold dynamics. Experimental access to this threshold dynamics is required in order to fully characterize neuronal input–output relationships. The challenge is practically intractable using present day experimental paradigms due to the cumulative, non-linear interactions involved. Here we introduce the Neuronal Response Clamp, a closed-loop technique enabling control over the instantaneous response probability of the neuron. The potential of the technique is demonstrated by showing direct access to threshold dynamics of cortical neuron in vitro using extracellular recording and stimulation, over timescales ranging from seconds to many hours. Moreover, the method allowed us to expose the sensitivity of threshold dynamics to spontaneous input from the network in which the neuron is embedded. The Response-Clamp technique follows the rationale of the voltage-clamp and dynamic-clamp approaches, extending it to the neuron's spiking behavior. The general framework offered here is applicable in the study of other neural systems, beyond the single neuron level.

Synthetic reverberating activity patterns are experimentally generated by stimulation of a subset of neurons embedded in a spontaneously active network of cortical cells in-vitro. The neurons are artificially connected by means of conditional stimulation matrix, forming a synthetic local circuit with a predefined programmable connectivity and time-delays. Possible uses of this experimental design are demonstrated, analyzing the sensitivity of these deterministic activity patterns to transmission delays and to the nature of ongoing network dynamics.

Distinct modules of the neural circuitry interact with each other and (through the motor-sensory loop) with the environment, forming a complex dynamic system. Neuro-prosthetic devices seeking to modulate or restore CNS function need to interact with the information flow at the level of neural modules electrically, bi-directionally and in real-time. A set of freely available generic tools is presented that allow computationally demanding multi-channel short-latency bi-directional interactions to be realized in in vivo and in vitro preparations using standard PC data acquisition and processing hardware and software (Mathworks Matlab and Simulink). A commercially available 60-channel extracellular multi-electrode recording and stimulation set-up connected to an ex vivo developing cortical neuronal culture is used as a model system to validate the method. We demonstrate how complex high-bandwidth (>10 MBit/s) neural recording data can be analyzed in real-time while simultaneously generating specific complex electrical stimulation feedback with deterministically timed responses at sub-millisecond resolution.

Wallach A, Marom S. Interactions between network synchrony and the dynamics of neuronal threshold. J Neurophysiol 107: 2926 -2936, 2012. First published March 7, 2012 doi:10.1152/jn.00876.2011.-Synchronous activity impacts on a range of functional brain capacities in health and disease. To address the interrelations between cellular level activity and network-wide synchronous events, we implemented in vitro a recently introduced technique, the response clamp, which enables online monitoring of single neuron threshold dynamics while ongoing network synchronous activity continues uninterrupted. We show that the occurrence of a synchronous network event causes a significant biphasic change in the single neuron threshold. These threshold dynamics are correlated across the neurons constituting the network and are entailed by the input to the neurons rather than by their own spiking (i.e., output) activity. The magnitude of network activity during a synchronous event is correlated with the threshold state of individual neurons at the event's onset. Recovery from the impact of a given synchronous event on the neuronal threshold lasts several seconds and seems to be a key determinant of the time to the next spontaneously occurring synchronous event. Moreover, the neuronal threshold is shown to be correlated with the excitability dynamics of the entire network. We conclude that the relations between the two levels (network activity and the single neuron threshold) should be thought of in terms that emphasize their interactive nature. neuron; response clamp; burst SYNCHRONY IS A MOST BASIC mode of activity in the cortex, believed to be critical for a range of functional brain capacities (Singer 1999). In most cases, regardless of the complex topology of connectivity (e.g., Eytan and Marom 2006;Bonifazi et al. 2009), the cortical synchronous event is considered a collective population phenomenon, emerging from interactions among the elements comprising the network (e.g., Abeles 1991; Beggs and Plenz 2003;Eckmann et al. 2010), rather than being driven by a uniquely identified class of pacing neurons. To address the generation of network-wide synchronous events, as well as the factors constraining the frequency of their occurrence, simultaneous monitoring of relevant state variables at both the network and cellular levels is wanted.While an ultimate design aiming at such multilevel monitoring would involve measurement and stimulation in the intact brain, obvious issues of experimental stability and control make the choice of large-scale networks of cortical neurons developing in vitro an attractive alternative in this context (Marom and Shahaf 2002). These networks are readily accessible to well-controlled long-term experiments and exhibit the dynamics of synchrony that is comparable in some key features to synchrony observed in vivo Ham et al. 2008;Jimbo et al. 1993;Maeda et al. 1995;Stegenga et al. 2008;Van Pelt et al. 2004;Wagenaar et al. 2006).Previous experiments that attempted simultaneous monitoring of both single ne...

Animals actively move their sensory organs in order to acquire sensory information. Some rodents, such as mice and rats, employ cyclic scanning motions of their facial whiskers to explore their proximal surrounding, a behavior known as whisking. Here, we investigated the contingency of whisking kinematics on the animal's behavioral context that arises from both internal processes (attention and expectations) and external constraints (available sensory and motor degrees of freedom). We recorded rat whisking at high temporal resolution in 2 experimental contexts-freely moving or head-fixed-and 2 spatial sensory configurations-a single row or 3 caudal whiskers on each side of the snout. We found that rapid sensorimotor twitches, called pumps, occurring during free-air whisking carry information about the rat's upcoming exploratory direction, as demonstrated by the ability of these pumps to predict consequent head and body locomotion. Specifically, pump behavior during both voluntary motionlessness and imposed head fixation exposed a backward redistribution of sensorimotor exploratory resources. Further, head-fixed rats employed a wide range of whisking profiles to compensate for the loss of head-and body-motor degrees of freedom. Finally, changing the number of intact vibrissae available to a rat resulted in an alteration of whisking strategy consistent with the rat actively reallocating its remaining resources. In sum, this work shows that rats adapt their active exploratory behavior in a homeostatic attempt to preserve sensorimotor coverage under changing environmental conditions and changing sensory capacities, including those imposed by various laboratory conditions.