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
P. Branchereau et al., 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, Synapse, 22(4), 1996, pp. 313-331
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.