The effects of arousal on apical amplification and conscious state

Abstract

Neocortical pyramidal cells can integrate two classes of input separately and use one to modulate response to the other. Their tuft dendrites are electrotonically separated from basal dendrites and soma by the apical dendrite, and apical hyperpolarization-activated currents (I_h) further isolate subthreshold integration of tuft inputs. When apical depolarization exceeds a threshold, however, it can enhance response to the basal inputs that specify the cell's selective sensitivity. This process is referred to as apical amplification (AA). We review evidence suggesting that, by regulating I_h in the apical compartments, adrenergic arousal controls the coupling between apical and somatic integration zones thus modifying cognitive capabilities closely associated with consciousness. Evidence relating AA to schizophrenia, sleep, and anesthesia is reviewed, and we assess theories that emphasize the relevance of AA to consciousness. Implications for theories of neocortical computation that emphasize context-sensitive modulation are summarized. We conclude that the findings concerning AA and its regulation by arousal offer a new perspective on states of consciousness, the function and evolution of neocortex, and psychopathology. Many issues worthy of closer examination arise.

Keywords: apical amplification; arousal; conscious state; context-sensitive modulation; hyperpolarization-activated currents; schizophrenia.

Figure 1.

Distribution of I_h and NE varicosities. (A) Left, Photomicrograph adapted from Audet et al. (1988) showing the distribution of noradrenergic varicosities (black dots) found throughout the neocortex. Right, immunocytochemical labeling of HCN (I_h) channels in the neocortex from Lörincz et al. (2001). (B) Schematic diagram of integration zones in L5 neocortical pyramidal neurons showing the areas of the dendrite that evoke Ca²⁺and NMDA spikes (Larkum et al., 2009). The graded shading and arrows denote the density of I_h-channels (gray) and NE receptors (NA) (yellow in the online version) embedded in the dendritic membrane of L5 neurons. (C) Schematic diagram of the distribution of NE varicosities found throughout the neocortex (black dots) relative to the distribution of I_h in pyramidal neurons (shown by shading of the dendrites).

Figure 2.

Primitive interactions from which neocortical circuits are built. The generic form of pyramidal cells is shown in a way that distinguishes their apical and basal trees. No attempt is made to show any columnar organization. The two cells shown in each of the six sections could be in either the same or different columns, or even in different cortical regions. They are shown at different heights in the diagram simply for diagrammatic convenience. Hyperpolarization-activated currents are shown as Ih. Inhibitory interneurons are shown as ovals. Cholinergic inputs are shown as ACh. Adrenergic inputs are shown as NE. Inputs from both of these subcortical modulatory systems tend to increase activation, and presumably in complementary ways. The outputs of individual neurons could combine these primitives in various ways. For example, the outputs of a given pyramidal cell could be excitatory at some of its projective sites and amplifying at others, or an inhibitory interneuron could combine disinhibition with dis-disamplification by inhibiting interneurons that target the soma as well as those that target the tuft.