title: Role of GABAA-Mediated Inhibition and Functional Assortment of Synapses onto Individual Layer 4 Neurons in Regulating Plasticity Expression in Visual Cortex.
abstract: Layer 4 (L4) of primary visual cortex (V1) is the main recipient of thalamocortical fibers from the dorsal lateral geniculate nucleus (LGNd). Thus, it is considered the main entry point of visual information into the neocortex and the first anatomical opportunity for intracortical visual processing before information leaves L4 and reaches supra- and infragranular cortical layers. The strength of monosynaptic connections from individual L4 excitatory cells onto adjacent L4 cells (unitary connections) is highly malleable, demonstrating that the initial stage of intracortical synaptic transmission of thalamocortical information can be altered by previous activity. However, the inhibitory network within L4 of V1 may act as an internal gate for induction of excitatory synaptic plasticity, thus providing either high fidelity throughput to supragranular layers or transmittal of a modified signal subject to recent activity-dependent plasticity. To evaluate this possibility, we compared the induction of synaptic plasticity using classical extracellular stimulation protocols that recruit a combination of excitatory and inhibitory synapses with stimulation of a single excitatory neuron onto a L4 cell. In order to induce plasticity, we paired pre- and postsynaptic activity (with the onset of postsynaptic spiking leading the presynaptic activation by 10ms) using extracellular stimulation (ECS) in acute slices of primary visual cortex and comparing the outcomes with our previously published results in which an identical protocol was used to induce synaptic plasticity between individual pre- and postsynaptic L4 excitatory neurons. Our results indicate that pairing of ECS with spiking in a L4 neuron fails to induce plasticity in L4-L4 connections if synaptic inhibition is intact. However, application of a similar pairing protocol under GABAARs inhibition by bath application of 2μM bicuculline does induce robust synaptic plasticity, long term potentiation (LTP) or long term depression (LTD), similar to our results with pairing of pre- and postsynaptic activation between individual excitatory L4 neurons in which inhibitory connections are not activated. These results are consistent with the well-established observation that inhibition limits the capacity for induction of plasticity at excitatory synapses and that pre- and postsynaptic activation at a fixed time interval can result in a variable range of plasticity outcomes. However, in the current study by virtue of having two sets of experimental data, we have provided a new insight into these processes. By randomly mixing the assorting of individual L4 neurons according to the frequency distribution of the experimentally determined plasticity outcome distribution based on the calculated convergence of multiple individual L4 neurons onto a single postsynaptic L4 neuron, we were able to compare then actual ECS plasticity outcomes to those predicted by randomly mixing individual pairs of neurons. Interestingly, the observed plasticity profiles with ECS cannot account for the random assortment of plasticity behaviors of synaptic connections between individual cell pairs. These results suggest that connections impinging onto a single postsynaptic cell may be grouped according to plasticity states.
authors: Virginia Tech Carillion Research Institute, 2 Riverside Circle, Roanoke, Virginia 24016, United States of America.
authors: Ignacio
authors: I
authors: Saez
authors: Virginia Tech Carillion Research Institute, 2 Riverside Circle, Roanoke, Virginia 24016, United States of America.
authors: Michael J
authors: MJ
authors: Friedlander
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D006168:Guinea Pigs; D017774:Long-Term Potentiation; D009473:Neuronal Plasticity / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011963:Receptors, GABA-A / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D014793:Visual Cortex / Q000502:physiology*
chemical_list: D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D001640:Bicuculline