PYRAMIDAL NEURONS IN RAT PREFRONTAL CORTEX SHOW A COMPLEX SYNAPTIC RESPONSE TO SINGLE ELECTRICAL-STIMULATION OF THE LOCUS-COERULEUS REGION - EVIDENCE FOR ANTIDROMIC ACTIVATION AND GABAERGIC INHIBITION USING IN-VIVO INTRACELLULAR-RECORDING AND ELECTRON-MICROSCOPY

Cognition and acquisition of novel motor skills and responses to emoti onal stimuli are thought to involve complex networking between pyramid al and local GABAergic neurons in the prefrontal cortex. There is incr easing evidence for the involvement of cortical norepinephrine (NE) de riving from the nucleus locus coeruleus (LC) in these processes, with possible reciprocal influence via descending projections from the pref rontal cortex to the region of the LC. We used in vivo intracellular r ecording in rat prefrontal cortex to determine the synaptic responses of individual neurons to single electrical stimulation of the mesencep halic region including the nucleus LC. The most common response consis ted of a late-IPSP alone or preceded by an EPSP. The presence of an ea rly-IPSP following the EPSP was sometimes detected. Analysis of the vo ltage dependence revealed that the late-IPSP and early-IPSP were putat ive K+- and Cl- dependent, respectively. Synaptic events occurred foll owing short delays and were inconsistent with the previously reported time for electrical activation of unmyelinated LC fibers. Moreover, sy stemic injection of the adrenergic antagonists propranolol (beta recep tors), or prazosin (alpha l receptors), did not block synaptic respons es to stimulation of the LC region. Finally, certain neurons were anti dromically activated following electrical stimulation of this region o f the dorsal pontine tegmentum. Taken together, these results suggest that the complex synaptic events in pyramidal neurons of the prefronta l cortex that are elicited by single electrical stimulation of the LC area are mainly due to antidromic activation of cortical efferents. Fu rther insight into the chemical circuitry underlying these complex syn aptic responses was provided by electron microscopic immunocytochemica l analysis of the relations between the physiologically characterized neurons and either 1) GABA or 2) dopamine-beta-hydroxylase (DBK), a ma rker for noradrenergic terminals. GABA-immunoreactive terminals formed numerous direct symmetric synapses on somata and dendrites of pyramid al cells recorded and filled with lucifer yellow (LY). In contrast, in single sections, noradrenergic terminals immunoreactive for DBH rarel y contacted LY-filled somata and dendrites. These results support the conclusion that IPSPs observed follow-ing single electrical stimulatio n of the LC region are mediated by GABA, with little involvement of NE . These IPSPs, arising from antidromic invasion of mPFC cells innervat ing the LC, may improve the signal-to-noise ratio and favor a better r esponsiveness of neighboring neurons to NE released in the mPFC. (C) 1 996 Wiley-Liss, Inc.