| Discovering the neural mechanisms underlying learning and memory is a critical issue within neuroscience. Synaptic plasticity is a likely candidate for mediating many forms of learning and memory---especially in the neocortex. Since this region's unique electrophysiological properties may play a unique role in learning and memory, knowledge of how synaptic number and structure change in the neocortex may be critical to understanding the link between synaptic structure and function. Towards this understanding, a meta-analysis (study 1) assessed several paradigms of behavioral plasticity, revealing consistent changes associated with enhanced neocortical activity, including increases in bouton size, multisynaptic terminals, axospinuous synapses, and vesicular content. Moreover, opposite changes (i.e., decreased bouton size, multisynaptic terminals, axospinuous synapses, and vesicular content) followed the deprivation of cortical activity. Given this a priori hypothesis for associating cortical synapse activity with morphology, manipulation of these activity levels (study 2) was conducted to verify whether analogous findings would be observed in a single population. Long-term potentiation (LTP) was induced in 6 chronically-implanted Long-Evans hooded rats and induction of long-term depression (LTD) was attempted in 6 additional rats. Six implanted rats served as controls. The induction of LTP resulted in an increase in cortical volume per neuron restricted to the region immediately adjacent to the potentiated site (upper Layer V), reflecting an increase in the number of excitatory axospinuous synapses per neuron. The induction of LTD failed, so these animals were treated as low-frequency stimulation controls. Surprisingly, these animals also produced an increase in cortical volume per neuron restricted to Layer V, caused by an increase in the number of excitatory axospinuous synapses. Thus, it seems that both high- and low-frequency stimulation fail to produce changes in morphology of Layer II/III synapses, despite the implication of synaptogenesis in this layer for behavioral plasticity. Although results are consistent with previous data reporting synaptogenesis following hippocampal LTP and (perhaps) cerebellar LTD, it is unclear how these low-frequency effects fit. Although multiple interpretations are possible, the results call into question any direct and simple relationship between changes in behavioral activity and synaptic plasticity. |
