Multiple Modes of Network Homeostasis in Visual Cortical Layer 2/3

Abstract

Sensory experience is crucial for shaping the cortical microcircuit during development and is thought to modify network function through several forms of Hebbian and homeostatic plasticity. Where and when these different forms of plasticity are expressed at particular synapse types within cortical microcircuits, and how they interact, is poorly understood. Here we investigated how two different visual deprivation paradigms, lid suture (LS) and intraocular TTX, affect the local microcircuit within layer 2/3 of rat visual cortex during the classical critical period for visual system plasticity. Both forms of visual deprivation produced a compensatory increase in the spontaneous firing of layer 2/3 pyramidal neurons in acute slices derived from monocular visual cortex. TTX increased spontaneous activity through an increase in the excitation/inhibition (E/I) balance within layer 2/3. In contrast, LS decreased the E/I balance by strongly depressing excitatory transmission, and the homeostatic increase in spontaneous activity was instead achieved through an increase in the intrinsic excitability of layer 2/3 pyramidal neurons. The microcircuit in layer 2/3 can thus use different forms of homeostatic plasticity to compensate for the loss of visual drive, depending on the specific demands produced by visual experience. The existence of multiple, partially redundant forms of homeostatic plasticity may ensure that network compensation can be achieved in response to a wide range of sensory perturbations.

Constitutively active H-ras accelerates multiple forms of plasticity in developing visual cortex

“…In contrast, mEPSP frequency decreased strongly after 3 d of MD in WT mice but returned to baseline levels after 6 d of MD. The initial decrease in mEPSP frequency is in agreement with a previous study (32), which showed that 3 d of monocular lid suture decreased mEPSC frequency by 33% in the monocular zone. Moreover, it suggests that release probability decreased during the first 3 d of MD, consistent with the previously reported presynaptic LTD mechanism for closedeye depression (16).…”

Delayed plasticity of inhibitory neurons in developing visual cortex

“…Intraocular TTX injection, lid suture, and dark rearing lead to a wide range of distinct changes in strengths of local connections among neurons in layers IV and II/III and in the intrinsic properties of those neurons in the monocular zone of the rat visual cortex before and at the beginning of the critical period (32,33). These changes do not account for the delayed plasticity of the visual responses of inhibitory neurons that we find in the binocular cortex in vivo.…”

“…Control (unmanipulated) animals were imaged at ages that spanned the critical period (postnatal days [25][26][27][28][29][30][31][32][33][34][35]. Imaging sessions began with intrinsic signal mapping of the binocular zone to locate the binocular portion of the primary visual cortex.…”

“…A purely Hebbian mechanism could never explain ocular dominance plasticity completely because it would make the deprived-eye responses disappear (30). Recent evidence indicates that the mechanism underlying nondeprived-eye response plasticity is distinct from these Hebbian changes (16,26,(31)(32)(33).…”

Synapse-type-specific plasticity in local circuits

“…However, the effect of sensory deprivation on STP is often inconsistent even for the same synapse type, with specific types of sensory deprivation promoting facilitation but others increasing depression [31 •• , [39][40][41][42][43]. A number of experimental factors, including the nature and age of deprivation [39,44] Similarly, preNMDARs influence STP at synapses from L4 neurons onto L2/3 pyramidal neurons, but not at L2/3 intralaminar synapses [47]. Development and sensory experience regulate pre-NMDAR expression, suggesting that these receptors are well suited for regulating synapse-type-specific STP [31 •• , 33,39,48].…”