Summary Neurons in sensory cortex integrate multiple influences to parse objects and support perception. Across multiple cortical areas, integration is characterized by two neuronal response properties: (1) surround suppression: modulatory contextual stimuli suppress responses to driving stimuli; (2) “normalization”: responses to multiple driving stimuli add sublinearly. These properties depend on input strength: for weak driving stimuli, contextual influences more weakly suppress or facilitate and summation becomes linear or supralinear. Understanding the circuit operations underlying integration is critical to understanding cortical function and disease. We present a simple, general theory. A wealth of integrative properties including the above emerge robustly from four properties of cortical circuitry: (1) supralinear neuronal input/output functions; (2) sufficiently strong recurrent excitation; (3) feedback inhibition; (4) simple spatial properties of intracortical connections. Integrative properties emerge dynamically as circuit properties, with excitatory and inhibitory neurons showing similar behaviors. In new recordings in visual cortex, we confirm key model predictions.

Summary It has been postulated that homeostatic mechanisms maintain stable circuit function by keeping neuronal firing within a set-point range, but such firing rate homeostasis has never been demonstrated in vivo. Here we use chronic multielectrode recordings to monitor firing rates in visual cortex of freely behaving rats during chronic monocular visual deprivation (MD). Firing rates in V1 were suppressed over the first 2 d of MD, but then rebounded to baseline over the next 2–3 d despite continued MD. This drop and rebound in firing was accompanied by bi-directional changes in mEPSC amplitude measured ex vivo. The rebound in firing was independent of sleep-wake state but was cell-type specific, as putative FS and regular spiking neurons responded to MD with different time-courses. These data establish for the first time that homeostatic mechanisms within the intact CNS act to stabilize neuronal firing rates in the face of sustained sensory perturbations.

SUMMARY Homeostatic mechanisms stabilize neural circuit function by keeping firing rates within a set-point range, but whether this process is gated by brain state is unknown. Here, we monitored firing rate homeostasis in individual visual cortical neurons in freely behaving rats as they cycled between sleep and wake states. When neuronal firing rates were perturbed by visual deprivation, they gradually returned to a precise, cell-autonomous set-point during periods of active wake, with lengthening of the wake period enhancing firing rate rebound. Unexpectedly, this resetting of neuronal firing was suppressed during sleep. This raises the possibility that memory consolidation or other sleep-dependent processes are vulnerable to interference from homeostatic plasticity mechanisms.

The onset of vision occurs when neural circuits in the visual cortex are immature, lacking the full complement of connections1,2 and the response selectivity that defines functional maturity3,4. Direction selective responses are particularly vulnerable to the effects of early visual deprivation, but how stimulus driven neural activity guides the emergence of cortical direction selectivity remains unclear. To explore this issue we developed a novel motion training paradigm that allowed us to monitor the impact of experience on the development of direction selective responses in visually naïve ferrets. Using intrinsic signal imaging techniques we found that training with a single axis of motion induced the rapid emergence of direction columns that were confined to cortical regions preferentially activated by the training stimulus. Using 2-photon calcium imaging techniques, we found that single neurons in visually naïve animals exhibited weak directional biases and lacked the strong local coherence in the spatial organization of direction preference that was evident in mature animals. Training with a moving stimulus, but not with a flashed stimulus, strengthened the direction selective responses of individual neurons and preferentially reversed the direction biases of neurons that deviated from their neighbors. Both effects contributed to an increase in local coherence. We conclude that early experience with moving visual stimuli drives the rapid emergence of direction selective responses in visual cortex.

Neurons in the visual cortex of all examined mammals exhibit orientation or direction tuning. New imaging techniques are allowing the circuit mechanisms underlying orientation and direction selectivity to be studied with clarity that was not possible a decade ago. However, these new techniques bring new challenges: robust quantitative measurements are needed to evaluate the findings from these studies, which can involve thousands of cells of varying response strength. Here we show that traditional measures of selectivity such as the orientation index (OI) and direction index (DI) are poorly suited for quantitative evaluation of orientation and direction tuning. We explore several alternative methods for quantifying tuning and for addressing a variety of questions that arise in studies on orientation- and direction-tuned cells and cell populations. We provide recommendations for which methods are best suited to which applications and we offer tips for avoiding potential pitfalls in applying these methods. Our goal is to supply a solid quantitative foundation for studies involving orientation and direction tuning.