Cortical Output Is Gated by Horizontally Projecting Neurons in the Deep Layers.

Pyramidal tract neurons (PTs) represent the major output cell type of the mammalian neocortex. Here, we report the origins of the PTs' ability to respond to a broad range of stimuli with onset latencies that rival or even precede those of their intracortical input neurons. We find that neurons with extensive horizontally projecting axons cluster around the deep-layer terminal fields of primary thalamocortical axons. The strategic location of these corticocortical neurons results in high convergence of thalamocortical inputs, which drive reliable sensory-evoked responses that precede those in other excitatory cell types. The resultant fast and horizontal stream of excitation provides PTs throughout the cortical area with input that acts to amplify additional inputs from thalamocortical and other intracortical populations. The fast onsets and broadly tuned characteristics of PT responses hence reflect a gating mechanism in the deep layers, which assures that sensory-evoked input can be reliably transformed into cortical output.

Cell type-specific three-dimensional structure of thalamocortical circuits in a column of rat vibrissal cortex.

Soma location, dendrite morphology, and synaptic innervation may represent key determinants of functional responses of individual neurons, such as sensory-evoked spiking. Here, we reconstruct the 3D circuits formed by thalamocortical afferents from the lemniscal pathway and excitatory neurons of an anatomically defined cortical column in rat vibrissal cortex. We objectively classify 9 cortical cell types and estimate the number and distribution of their somata, dendrites, and thalamocortical synapses. Somata and dendrites of most cell types intermingle, while thalamocortical connectivity depends strongly upon the cell type and the 3D soma location of the postsynaptic neuron. Correlating dendrite morphology and thalamocortical connectivity to functional responses revealed that the lemniscal afferents can account for some of the cell type- and location-specific subthreshold and spiking responses after passive whisker touch (e.g., in layer 4, but not for other cell types, e.g., in layer 5). Our data provides a quantitative 3D prediction of the cell type-specific lemniscal synaptic wiring diagram and elucidates structure-function relationships of this physiologically relevant pathway at single-cell resolution.

Driver or coincidence detector: modal switch of a corticothalamic giant synapse controlled by spontaneous activity and short-term depression.

Giant synapses between layer 5B (L5B) neurons of somatosensory (barrel) cortex and neurons of the posteromedial nucleus (POm) of thalamus reside in a key position of the cortico-thalamo-cortical (CTC) loop, yet their synaptic properties and contribution to CTC information processing remain poorly understood. Fluorescence-guided local stimulation of terminals were combined with postsynaptic whole-cell recordings in thalamus to study synaptic transmission at an identified giant synapse. We found large EPSCs mediated by Ca(2+)-permeable AMPA and NMDA receptors. A single presynaptic electrical stimulus evoked a train of postsynaptic action potentials, indicating that a single L5B input can effectively drive the thalamic neuron. Repetitive stimulation caused strong short-term depression (STD) with fast recovery. To examine how these synaptic properties affect information transfer, spontaneous and evoked activity of L5B neurons was recorded in vivo and played back to giant terminals in vitro. We found that suprathreshold synaptic transmission was suppressed because of spontaneous activity causing strong STD of the L5B-POm giant synapse. Thalamic neurons only spiked after intervals of presynaptic silence or when costimulating two giant terminals. Therefore, STD caused by spontaneous activity of L5B neurons can switch the synapse from a "driver mode" to a "coincidence mode." Mechanisms decreasing spontaneous activity in L5B neurons and inputs synchronized by a sensory stimulus may thus gate the cortico-thalamo-cortical loop.

NMDA receptors induce somatodendritic secretion in hypothalamic neurones of lactating female rats.

Many neurones in the mammalian brain are known to release the content of their vesicles from somatodendritic locations. These vesicles usually contain retrograde messengers that modulate network properties. The back-propagating action potential is thought to be the principal physiological stimulus that evokes somatodendritic release. In contrast, here we show that calcium influx through NMDA receptor (NMDAR) channels, in the absence of postsynaptic cell firing, is also able to induce vesicle fusion from non-synaptic sites in nucleated outside-out patches of dorsomedial supraoptic nucleus (SON) neurones of adult female rats, in particular during their reproductive stages. The physiological significance of this mechanism was characterized in intact brain slices, where NMDAR-mediated release of oxytocin was shown to retrogradely inhibit presynaptic GABA release, in the absence of postsynaptic cell firing. This implies that glutamatergic synaptic input in itself is sufficient to elicit the release of oxytocin, which in turn acts as a retrograde messenger leading to the depression of nearby GABA synapses. In addition, we found that during lactation, when oxytocin demand is high, NMDA-induced oxytocin release is up-regulated compared to that in non-reproductive rats. Thus, in the hypothalamus, local signalling back and forth between pre- and postsynaptic compartments and between different synapses may occur independently of the firing activity of the postsynaptic neurone.