Figure 14.

Schematic model that illustrates the state-dependent bi-directional D1/D5R modulation of L-type Ca²⁺ potentials through PKA potentiation and PKC suppression. Functional incoming synaptic signals to the distal dendrites and reaching the soma represent numerous temporally and spatially contiguous synaptic signals from diverse inputs. Such synaptic signals can be categorized as either strong or weak inputs, evoking suprathreshold Ca²⁺ spikes and plateaus or subthreshold hump potentials, respectively. A critical frequency of back-propagating Na⁺ spikes can evoke large, regenerative, voltage-gated Ca²⁺ spikes in the distal dendritic initiation zone (Schiller et al., 1997; Larkum et al., 1999a), whereas a single back-propagating Na⁺ spike generated in the axon facilitates the initiation of voltage-gated Ca²⁺ spikes when it is coincidental with synaptic input to the same distal dendritic site (Larkum et al., 1999b). For synaptic integration, the timing and location of evoked voltage-gated Ca²⁺ responses in dendrites by strong or weak inputs is important (Oakley et al., 2001). Nevertheless, an active participation of dendritic Ca²⁺ in amplifying distal inputs may occur mainly when powerful repolarizing dendritic K⁺ channels are suppressed (Gonzalez-Burgos and Barrionuevo, 2001). Dopamine D1/D5 receptor activation is known to suppress several subtypes of soma-dendritic K⁺ currents (Kitai and Surmeier, 1993; Nisenbaum et al., 1998; Dong and White, 2003), thus enabling the actions of dendritic Ca²⁺ potential to contribute actively in synaptic signal amplification and integration. A, Weak synaptic inputs lead to weak dendritic depolarizations that frequently evoke Ca²⁺ hump potentials that are subthreshold to evoking a suprathreshold Ca²⁺ spike (Seamans et al., 1997). B, D1/D5R activation results in a transient amplification or “boost” of the weak synaptic signal through a D1R-G_s-PKA pathway that potentiates L-type Ca²⁺ channels over time. C, The D1/D5R-PKA potentiation of the Ca²⁺ hump led to full Ca²⁺ spike firing via L-type Ca²⁺ channel activation in soma-proximal-basal dendrites. This Ca²⁺ spike firing is temporary, however, because it is eventually suppressed as greater Ca²⁺ influx activates a Ca²⁺-dependent D1-G_q-calcyon-PKC suppression of the L-type Ca²⁺ channel, thereby reducing Ca²⁺ influx (A). D, On the other hand, incoming strong synaptic inputs or back-propagating Na⁺ spikes can evoke full suprathreshold Ca²⁺ spikes. Optimal stimulation of D1/D5R via a [Ca²⁺]i-dependent D1-G_q-calcyon-PKC mechanism may lead to a differential suppression of the L-type Ca²⁺ channel-mediated Ca²⁺ spikes in various regions of the dendrites. This may serve functionally to “sharpen” incoming synaptic signals before they are integrated in the soma. Strong stimulation of D1/D5 receptor leads to severe suppression of dendritic Ca²⁺ spikes and may serve to prevent any synaptic signals from being integrated or amplified.