The α_2A‐adrenoceptor suppresses excitatory synaptic transmission to both excitatory and inhibitory neurons in layer 4 barrel cortex

Abstract

The mammalian neocortex is widely innervated by noradrenergic (NA) fibres from the locus coeruleus. To determine the effects of NA on vertical synaptic inputs to layer 4 (L4) cells from the ventrobasal thalamus and layer 2/3 (L2/3), thalamocortical slices were prepared and whole-cell recordings were made from L4 cells. Excitatory synaptic responses were evoked by electrical stimulation of the thalamus or L2/3 immediately above. Recorded cells were identified as regular spiking, regular spiking non-pyramidal or fast spiking cells through their firing patterns in response to current injections. NA suppressed (∼50% of control) excitatory vertical inputs to all cell types in a dose-dependent manner. The presynaptic site of action of NA was suggested by three independent studies. First, responses caused by iontophoretically applied glutamate were not suppressed by NA. Second, the paired pulse ratio was increased during NA suppression. Finally, a coefficient of variation (CV) analysis was performed and the resultant diagonal alignment of the ratio of CV plotted against the ratio of the amplitude of postsynaptic responses suggests a presynaptic mechanism for the suppression. Experiments with phenylephrine (an α -agonist), prazosin (an α -antagonist), yohimbine (an α -antagonist) and propranolol (a β-antagonist) indicated that suppression was mediated by the α -adrenoceptor. To determine whether the α -adrenoceptor subtype was involved, α -adrenoceptor knockout mice were used. NA failed to suppress EPSCs in all cell types, suggesting an involvement of the α -adrenoceptor. Altogether, we concluded that NA suppresses vertical excitatory synaptic connections in L4 excitatory and inhibitory cells through the presynaptic α -adrenoceptor.

Apical drive—A cellular mechanism of dreaming?

“…Acting via ɑ receptors (ɑAR), NA may suppress excitatory synapses during wake, preferentially in Layer 1, where NA fibers are most dense (Audet et al, 1988). This may selectively weaken the excitatory apical input (Boehm, 1999: Jiménez-Rivera et al, 2012Ohshima et al, 2017), thus preventing apical input from alone driving the cell in the wake state. Thus, high NA suppressing apical input may help explain why we do not dream in the wake state.…”

A Hypothetical Model Concerning How Spike-Timing-Dependent Plasticity Contributes to Neural Circuit Formation and Initiation of the Critical Period in Barrel Cortex

“…Unlike L2/3, direct connections from L4 neurons in spared barrels are rare (Petersen and Sakmann, 2000). However, in electrophysiological experiments, stimulation of L2/3 induces monosynaptic EPSPs in the excitatory cells in the L4 barrel of the same column (Schubert et al, 2003;Ohshima et al, 2017). Thus, horizontal spread in L2/3 may ultimate induce spiking in L4 (Tanifuji et al, 1994), although anatomically, there are few, if any, direct connections from L2/3 to L4 in the same column (Burkhalter, 1989).…”

Neuromodulation influences synchronization and intrinsic read-out

“…The role of presynaptic neuromodulation in suppressing cortical connections 11 , 12 and changing attractor states 47 , as well as allowing rapid synaptic weight changes 20 has previously been assessed. Theoretical work has also emphasized the connection between correlations and information content 34 , 48 – 50 .…”