DOPAMINE D1/5 RECEPTOR-MEDIATED LTP OF INTRINSIC EXCITABILITY IN RAT PREFRONTAL CORTICAL NEURONS: Ca-DEPENDENT INTRACELLULAR SIGNALING

Prefrontal Cortex (PFC) dopamine D1/5 receptors modulate long-and short-term neuronal plasticity which may contribute to cognitive functions. Synergistic to synaptic strength modulation, direct post-synaptic D1/5 receptor activation also modulates voltage-dependent ionic currents that regulate spike firing, thus altering the neuronal input-output relationships in a process called long-term potentiation of intrinsic excitability (LTP-IE). Here, the intracellular signals that mediate this D1/5 receptor-dependent LTP-IE were determined using whole-cell current-clamp recordings in layer V-VI rat pyramidal neurons from PFC slices. Following blockade of all major amino acid receptors (V HOLD =-65mV) brief tetanic stimulation (20 Hz) of local afferents or application of the D1 agonist SKF81297 (0.2–50µM) induced LTP-IE, as shown by a prolonged (>40mins) increase in depolarizing pulse-evoked spike firing.