Binocular input coincidence mediates critical period plasticity in the mouse primary visual cortex.

Classical studies on the development of ocular dominance (OD) organization in primary visual cortex (V1) have revealed a postnatal critical period (CP), during which visual inputs between the two eyes are most effective in shaping cortical circuits through synaptic competition. A brief closure of one eye during CP caused a pronounced shift of response preference of V1 neurons toward the open eye, a form of CP plasticity in the developing V1. However, it remains unclear what particular property of binocular inputs during CP is responsible for mediating this experience-dependent OD plasticity. Using whole-cell recording in mouse V1, we found that visually driven synaptic inputs from the two eyes to binocular cells in layers 2/3 and 4 became highly coincident during CP. Enhancing cortical GABAergic transmission activity by brain infusion with diazepam not only caused a precocious onset of the high coincidence of binocular inputs and OD plasticity in pre-CP mice, but rescued both of them in dark-reared mice, suggesting a tight link between coincident binocular inputs and CP plasticity. In Thy1-ChR2 mice, chronic disruption of this binocular input coincidence during CP by asynchronous optogenetic activation of retinal ganglion cells abolished the OD plasticity. Computational simulation using a feed-forward network model further suggests that the coincident inputs could mediate this CP plasticity through a homeostatic synaptic learning mechanism with synaptic competition. These results suggest that the high-level correlation of binocular inputs is a hallmark of the CP of developing V1 and serves as neural substrate for the induction of OD plasticity.

Synaptic mechanisms of direction selectivity in primary auditory cortex.

Frequency modulation (FM) is a prominent feature in animal vocalization and human speech. Although many neurons in the auditory cortex are known to be selective for FM direction, the synaptic mechanisms underlying this selectivity are not well understood. Previous studies of both visual and auditory neurons have suggested two general mechanisms for direction selectivity: (1) differential delays of excitatory inputs across the spatial/spectral receptive field and (2) spatial/spectral offset between excitatory and inhibitory inputs. In this study, we have examined the contributions of both mechanisms to FM direction selectivity in rat primary auditory cortex. The excitatory and inhibitory synaptic inputs to each cortical neuron were measured by in vivo whole-cell recording. The spectrotemporal receptive field of each type of inputs was mapped with random tone pips and compared with direction selectivity of the neuron measured with FM stimuli. We found that both the differential delay of the excitatory input and the spectral offset between excitation and inhibition are positively correlated with direction selectivity of the neuron. Thus, both synaptic mechanisms are likely to contribute to FM direction selectivity in the auditory cortex. Finally, direction selectivity measured from the spiking output is significantly stronger than that based on the subthreshold membrane potentials, indicating that the selectivity is further sharpened by the spike generation mechanism.

Coincidence detection of synaptic inputs is facilitated at the distal dendrites after long-term potentiation induction.

Two major aspects of dendritic integration, coincidence detection and temporal integration, depend critically on the spatial and temporal properties of the dendritic summation of synaptic inputs. Neuronal activity capable of inducing synaptic long-term potentiation (LTP) leads to increased linearity of the spatial summation of synchronous EPSPs. Whether such activity can also modulate the temporal summation of EPSPs is unknown. In the present study, we examined the linearity of the summation of EPSPs spaced by different time intervals in hippocampal CA1 pyramidal neurons, before and after LTP induction. We found that LTP induction resulted in an increased linearity of summation of the potentiated input with another synchronous or asynchronous input, with a striking dendritic location-specific selectivity for the timing of the summed inputs. At distal dendrites, LTP induction led to an increased linearity of summation only for EPSPs arriving within 5 ms, thus favoring the summation of coincident inputs. In contrast, LTP induction at proximal dendrites increased the linearity of summation for EPSPs arriving within a time window of >20 ms. Furthermore, for synaptic inputs at the distal dendrite, enhanced spiking output after LTP induction was observed only for coincidently summed EPSPs, suggesting facilitated coincidence detection. In contrast, for proximal inputs, enhanced spiking output after LTP induction occurred for EPSPs arriving within a broader time window of approximately 20 ms, favoring temporal integration. Such dendritic location-dependent differential modulation of coincidence detection and temporal integration by neuronal activity represents a form of activity-dependent and domain-specific plasticity in the function of dendritic information processing.

ATP released by astrocytes mediates glutamatergic activity-dependent heterosynaptic suppression.

Extracellular ATP released from axons is known to assist activity-dependent signaling between neurons and Schwann cells in the peripheral nervous system. Here we report that ATP released from astrocytes as a result of neuronal activity can also modulate central synaptic transmission. In cultures of hippocampal neurons, endogenously released ATP tonically suppresses glutamatergic synapses via presynaptic P2Y receptors, an effect that depends on the presence of cocultured astrocytes. Glutamate release accompanying neuronal activity also activates non-NMDA receptors of nearby astrocytes and triggers ATP release from these cells, which in turn causes homo- and heterosynaptic suppression. In CA1 pyramidal neurons of hippocampal slices, a similar synaptic suppression was also produced by adenosine, an immediate degradation product of ATP released by glial cells. Thus, neuron-glia crosstalk may participate in activity-dependent synaptic modulation.