It's about time for thalamocortical circuits

Abstract

The timing of thalamocortical excitation and inhibition is critical to local microcircuits. Two new papers shed light on the development and performance of a somatosensory microcircuit that regulates the integration of thalamic inputs.

Figure 1

Development and function of the thalamocortical microcircuit. (a) The emergence of feedforward inhibition. In the neonatal mouse, thalamic (thalamocortical) afferents entering the somatosensory cortex excite cortical projection neurons (principal cells, PrN) in layer 4. They also provide weak excitation to GABAergic fast-spiking interneurons. In turn, fast-spiking interneurons make sparse, weak synapses onto PrNs that evoke GABAergic depolarizing postsynaptic potentials. In response to thalamic stimulation (lower), PrNs respond with a simple EPSP. (b) The properties of this thalamocortical microcircuit change rapidly and dramatically after P6. Now, thalamocortical afferents strongly excite fast-spiking neurons (in fact, more strongly than PrNs). Fast-spiking neurons also make powerful and abundant connections onto PrNs, and GABA release evokes inhibitory postsynaptic potentials (IPSPs). Thus, thalamocortical activity (lower) evokes a standard, mature EPSP-IPSP sequence in PrNs after P6 (compare with EPSP only, gray dashed line). (c) The first 3 ms of cortical sensory processing. Time 0: thalamocortical afferents excite fast-spiking cells and PrNs. The activation of a large and fast excitatory postsynaptic conductance (G_e) onto fast-spiking neurons leads to a rapid depolarization of the membrane potential (V_m). At around 0.6 ms, this generates a spike. Meanwhile, V_m rises more slowly in PrNs as a result of a slower G_e (measured at the soma) and longer membrane time constant. Time 1.2 ms: GABA released from fast-spiking interneurons initiates a GABA_A receptor–mediated conductance (G_i) in PrNs. Time 2.7 ms: G_i reaches its peak. By counteracting G_e, G_i hyperpolarizes Vm to conclude the standard EPSP-IPSP sequence. If PrNs do not reach threshold for spike generation before the onset of the IPSP, they likely never will (at least in the immediate future).