Neural plasticity without postsynaptic action potentials: less-active inputs become dominant when kitten visual cortical cells are pharmacologically inhibited.

Abstract

Models of synaptic plasticity in the nervous system have conventionally assumed a mechanism in which spike activity of a postsynaptic cell enhances the efficacy of recently active presynaptic inputs. Making use of the prompt and dramatic response of the visual cortex to occlusion of vision in one eye during the critical period, we tested the role of postsynaptic activity in ocular dominance plasticity. To do so, we selectively blocked cortical cell discharges with a continuous intracortical infusion of the inhibitory neurotransmitter agonist muscimol during a period of monocular deprivation. This drug inhibits cortical cell discharges with no apparent effect on the activity of their presynaptic geniculocortical inputs. Recording from single cortical cells after they had recovered from the muscimol-induced blockade, we found a consistent shift in the responsiveness of the visual cortex in favor of the less-active, closed eye, while the normal shift in favor of the more-active, open eye was evident in regions not affected by the treatment. Such an inhibition-coupled expression of plasticity in favor of the less-active, closed eye cannot be explained by a nonspecific disruption of cortical function. We interpret these results to indicate (i) that the postsynaptic cell is crucially involved in plasticity of the visual cortex, (ii) that the direction of cortical plasticity depends on postsynaptic membrane conductance or polarization, and (iii) that plasticity can occur in the absence of postsynaptic spike activity.Synaptic plasticity is known to be widespread in both the developing and the mature central nervous system. A hypothesis about the mechanism of plasticity in development, put forward by Hebb, is that spike activity in the postsynaptic cell enhances the efficacy of recently active inputs (1-6). Hebb's hypothesis has been used to explain many instances of neural plasticity (7). This hypothesis stands in contrast to one favoring a purely presynaptic mechanism, as was reported for classical conditioning in Aplysia, in which responses of cells were facilitated even while their somata were hyperpolarized by an intracellular microelectrode (8).In the visual (9-14) and motor cortices (15), however, several types of evidence favor an excitation-coupled postsynaptic mechanism of plasticity.Synaptic connections serving the two eyes to the visual cortex are reorganized during normal development (16-18).This reorganization is most dramatic when vision in one eye is occluded during a critical period in early life (17)(18)(19)(20): the occluded eye loses its ability to drive most cortical cells, which come to respond exclusively to the nonoccluded eye. This phenomenon is called ocular dominance plasticity.Previous experiments in which a region of visual cortex was infused with tetrodotoxin during a period of monocular deprivation demonstrated that activity at the level of the visual cortex is crucial for ocular dominance plasticity (10). Because tetrodotoxin blocks pre-as well as postsynaptic activities in the vis...

Cellular mechanisms of visual cortical plasticity: a game of cat and mouse.

“…Infusion of the GABA A receptor agonist muscimol, which blocks only postsynaptic activity, reverses the direction of plasticity induced by lid suture. Inputs from the deprived eye, better correlated with the inactivated cortical cells, strengthen physiologically and expand anatomically (Reiter and Stryker 1988;Hata and Stryker 1994). These effects of muscimol demonstrate a role for the postsynaptic, cortical cell in determining the direction of ocular dominance plasticity, and confirm its Hebbian nature.…”

“…Calcium activates oLCaMKII, and either calcium or depolarization activates some parallel pathway, both of which are likely involved in the resultant plasticity (Gordon et al 1996a). Modulatory neurotransmitter systems and GABA-mediated inhibition probably affect plasticity by facilitating and inhibiting depolarization, respectively (Reiter and Stryker 1988;Bear and Singer 1986;Singer 1993, 1995;Hata and Stryker 1994). Neurotrophins might function as growth-promoting signals to geniculocortical afferents and cortical neurons (McAllister et al 1995;Riddle et al 1995;Boenhoeffer 1996;Cabelli et al 1996;Ghosh 1996) and/or as facilitators of modulatory neurotransmission (Mafei et al 1992; Thoenen 1995).…”

The Formation of Cooperative Cell Assemblies in the Visual Cortex

“…They can account for the changes of synaptic transmission that occur in response to monocular deprivation and reverse suture. Moreover, the results on homosynaptic depression provide an explanation for the paradoxical observation that the afferents from the open eye can become weakened rather than strengthened if cortical neurons are exposed to high concentrations of 5-amino-phosphono-valeriate (APV) (Bear et al 1990) or the y-aminobutyric acid (GABA) receptor agonist muscimol (Reiter and Stryker, 1988). Such a modification is expected if the afferents from the open eye reach the threshold for homosynaptic depression but fail to activate NMDA-receptor-gated channels.…”

Spike-timing dependent plasticity as a mechanism for ocular dominance shift

“…Depriving one eye of light (monocular deprivation, or MD) causes the OD columns corresponding to the non-deprived eye to expand, while deprived-eye OD columns shrink. Postsynaptic activity is necessary for OD shift [13], consistent with Hebbian learning, but the mechanisms through which OD shift occurs remain unclear.…”