Evidence for homeostatic adjustments of rat somatosensory cortical neuronsto changes in extracellular acetylcholine concentrations produced by iontophoretic administration of acetylcholine and by systemic diisopropylfluorophosphate treatment
G. Testylier et al., Evidence for homeostatic adjustments of rat somatosensory cortical neuronsto changes in extracellular acetylcholine concentrations produced by iontophoretic administration of acetylcholine and by systemic diisopropylfluorophosphate treatment, NEUROSCIENC, 91(3), 1999, pp. 843-870
We describe the responses of single units in the awake (24 cells) or uretha
ne-anesthetized (37 cells) rat somatosensory cortex during repeated iontoph
oretic pulses (1.0 s, 85 nA) of acetylcholine, both before and after system
ic treatment with the irreversible acetylcholinesterase inhibitor diisoprop
ylfluorophosphate (i.p., 0.3-0.5 LD50). The time-course of the response to
acetylcholine pulses differed among cortical neurons but was characteristic
for a given cell. Different time-courses included monophasic excitatory or
inhibitory responses, biphasic (excitatory-inhibitory, inhibitory-excitato
ry, excitatory-excitatory, and inhibitory-inhibitory), and triphasic (excit
atory-excitatory-inhibitory, inhibitory-inhibitory-excitatory, and inhibito
ry-excitatory-inhibitory) responses. Although the sign and time-course of t
he individual responses remained consistent, their magnitude fluctuated acr
oss time; most cells exhibited either an initial increase or decrease in re
sponse magnitude followed by oscillations in magnitude that diminished with
time, gradually approaching the original size. The time-course of the char
acteristic response to an acetylcholine pulse appeared to determine directi
on and rate of change in response magnitude with successive pulses of acety
lcholine. Diisopropylfluorophosphate treatment, given Ih after beginning re
peated acetylcholine pulses, often resulted in a gradual increase in sponta
neous activity to a slightly higher but stable level. Superimposed on this
change in background activity, the oscillations in the response amplitude r
eappeared and then subsided in a pattern similar to the decay seen prior to
diisopropylfluorophosphate treatment.
Our results suggest that dynamic, homeostatic mechanisms control neuronal e
xcitability by adjusting the balance between excitatory and inhibitory infl
uences within the cortical circuitry and that these mechanisms are engaged
by prolonged increases in extracellular acetylcholine levels caused by repe
ated pulses of acetylcholine and by acetylcholinesterase inhibition. Howeve
r, this ability of neurons in the cortical neuronal network to rapidly adju
st to changes in extracellular levels of acetylcholine questions the potent
ial efficacy of therapeutic treatments designed to increase ambient levels
of acetylcholine as a treatment for Alzheimer's disease or to enhance mecha
nisms of learning and memory. (C) 1999 IBRO. Published by Elsevier Science
Ltd.