GABAB receptor-dependent bidirectional regulation of critical period ocular dominance plasticity in cats.

Gama amino butyric acid (GABA) inhibition plays an important role in the onset and offset of the critical period for ocular dominance (OD) plasticity in the primary visual cortex. Previous studies have focused on the involvement of GABAA receptors, while the potential contribution of GABAB receptors to OD plasticity has been neglected. In this study, the GABAB receptor antagonist SCH50911 or agonist baclofen was infused into the primary visual cortex of cats concurrently with a period of monocular deprivation (MD).

Critical periods: motion sensitivity is early in all areas.

Recent work shows that global motion sensitivity, a property of extrastriate cortex, can be altered by early visual deprivation, while binocularity, a property of primary visual cortex, is still plastic. This contradicts the hypothesis that critical periods end later at higher levels of the system.

The foundations of development and deprivation in the visual system.

The pioneering work of Torsten Wiesel and David Hubel on the development and deprivation of the visual system will be summarised, together with some comments on their influence, and some personal reminiscences by the author.

Experience-driven plasticity of visual cortex limited by myelin and Nogo receptor.

Monocular deprivation normally alters ocular dominance in the visual cortex only during a postnatal critical period (20 to 32 days postnatal in mice). We find that mutations in the Nogo-66 receptor (NgR) affect cessation of ocular dominance plasticity. In NgR-/- mice, plasticity during the critical period is normal, but it continues abnormally such that ocular dominance at 45 or 120 days postnatal is subject to the same plasticity as at juvenile ages.

Reversible blockade of experience-dependent plasticity by calcineurin in mouse visual cortex.

Numerous protein kinases have been implicated in visual cortex plasticity, but the role of serine/threonine protein phosphatases has not yet been established. Calcineurin, the only known Ca2+/calmodulin-activated protein phosphatase in the brain, has been identified as a molecular constraint on synaptic plasticity in the hippocampus and on memory. Using transgenic mice overexpressing calcineurin inducibly in forebrain neurons, we now provide evidence that calcineurin is also involved in ocular dominance plasticity.

Requirement for the RIIbeta isoform of PKA, but not calcium-stimulated adenylyl cyclase, in visual cortical plasticity.

The cAMP-dependent protein kinase (PKA) signaling pathway plays a key role in visual cortical plasticity. Inhibitors that block activation of all PKA regulatory subunits (RIalpha,RIbeta, RIIalpha, RIIbeta) abolish long-term potentiation (LTP) and long-term depression (LTD) in vitro and ocular dominance plasticity (ODP) in vivo. The details of this signaling cascade, however, including the source of PKA signals and which PKA subunits are involved, are unknown.

Reduced ocular dominance plasticity and long-term potentiation in the developing visual cortex of protein kinase A RII alpha mutant mice.

The cAMP-dependent protein kinase (PKA) signalling pathway has been shown to play an important role in long-term potentiation (LTP) and depression (LTD), and ocular dominance plasticity in the visual cortex. In order to investigate further the involvement of individual PKA subunits in visual cortical plasticity, LTP and LTD in vitro and ocular dominance plasticity in vivo in the developing visual cortex were examined in mice lacking the RII alpha subunit of PKA. Here we show that LTP in layers II/III was decreased in RII alpha knockout mice, but LTD was almost unaffected, and the ocular dominance shift induced by monocular deprivation was also partially blocked.

Layer variations of long-term depression in rat visual cortex.

In vitro long-term depression (LTD) is thought to be a model for the loss of cortical responsiveness to an eye deprived of vision during the critical period. Using whole cell recording, the present study investigates the mechanisms of LTD in vitro across layers in developing rat visual cortex. LTD was induced in layers II/III, V, and VI but not layer IV with 10-min 1-Hz stimulation paired with postsynaptic depolarization.

Blockade of cyclic AMP-dependent protein kinase does not prevent the reverse ocular dominance shift in kitten visual cortex.

Monocular deprivation (MD) during the critical period for the development of visual cortex causes a loss of binocular response of neurons and a shift to the open eye, a normal ocular dominance (OD) shift. However, when MD is combined with chronic inactivation of the visual cortex by muscimol, the OD distribution of the neurons shifts to the deprived eye (reverse OD shift). We have previously shown that the normal OD shift is abolished by chronic infusion of the protein kinase A (PKA) inhibitor, 8-chloroadenosine-3', 5'-cyclic monophosphorothioate, Rp-isomer (Rp-8-Cl-cAMPS), into kitten visual cortex.

Orientation selectivity is reduced by monocular deprivation in combination with PKA inhibitors.

We have previously shown that the protein kinase A (PKA) inhibitor, 8-chloroadenosine-3',5'-monophosphorothioate (Rp-8-Cl-cAMPS), abolishes ocular dominance plasticity in the cat visual cortex. Here we investigate the effect of this inhibitor on orientation selectivity. The inhibitor reduces orientation selectivity in monocularly deprived animals but not in normal animals.

cGMP-induced presynaptic depression and postsynaptic facilitation at glutamatergic synapses in visual cortex.

The mechanisms by which the intracellular messenger cGMP can modulate synaptic efficacy remain poorly understood. Here we report that cGMP, acting through cGMP-dependent protein kinase (PKG), has multiple rapid and reversible effects on synaptic transmission in slices and cultures of rodent visual cortex. Extracellular application of the membrane permeable cGMP analog 8-bromoguanosine-3',5'-cyclic monophosphate (8-Br-cGMP) and the PKG specific activator beta-phenyl-1,N2-etheno-8-bromoguanosine-3',5'-cyclic monophosphorothioate sp-isomer (Sp-8-Br-PET-cGMPS) reduced stimulus-evoked EPSPs in slices.