Chronic cold stress increases excitatory effects of norepinephrine on spontaneous and evoked activity of basolateral amygdala neurons

Abstract

Neurons of the amygdala respond to a variety of stressors. The basolateral amygdala (BLA) receives dense norepinephrine (NE) innervation from the locus coeruleus, and stressful and conditioned stimuli cause increases in NE levels within the BLA. Furthermore, chronic stress exposure leads to sensitization of the stress response. The actions of NE in different structures involved in the stress circuit have been shown to play a role in this sensitization response. Here, we examine how chronic cold stress alters NE modulation of spontaneous and evoked activity in the BLA. In controls, NE inhibited spontaneous firing in the majority of BLA neurons, with some neurons showing excitation at lower doses and inhibition at higher doses of NE. NE also decreased the responsiveness of these neurons to electrical stimulation of the entorhinal and sensory association cortices. After chronic cold exposure, NE caused increases in spontaneous activity in a larger proportion of BLA neurons than in controls, and now produced a facilitation of responses evoked by stimulation of entorhinal and sensory association cortical inputs. These studies show that chronic cold exposure leads to an increase in the excitatory effects of NE on BLA neuronal activity, and suggest a mechanism by which organisms may display an enhancement of hormonal, autonomic, and behavioural responses to acute stressful stimuli after chronic stress exposure.

Figure 1

Chronic cold exposure does not affect spontaneous firing rates of neurons within the BLA. Spontaneous firing rates of neurons from control rats, rats exposed to 7 days of cold, and rats exposed to 14 days of cold. Large diamonds represent group averages, small diamonds represent individual neurons.

Figure 2

Noradrenergic modulation of spontaneous activity in BLA neurons is altered after fourteen days of chronic cold exposure, but not seven. A) Example of a neuron from a control rat showing an inhibition in spontaneous activity during microiontophoresis of NE. B) Example of a neuron from a 14 day cold-exposed rat displaying an excitation of spontaneous activity during microiontophoresis of NE. C) Neurons from control rats and rats exposed to seven days of cold showed primarily inhibitory responses to NE, however in rats exposed to 14 days of cold, more neurons display excitatory responses to NE.

Figure 3

Noradrenergic modulation of spontaneous activity in BLA projection neurons is altered after fourteen days of chronic cold exposure, but not seven. A) Electrophysiological trace of a BLA neuron displaying an antidromic spike in response to entorhinal cortical stimulation. Note the constant latency of the onset of the response. B) All BLA neurons confirmed as projection cells via antidromic activation from control and seven day cold-exposed rats were inhibited by microiontophoresis of NE. However, while a subset of neurons from rats exposed to 14 days of cold also displayed an inhibition, others displayed excitatory responses to NE iontophoresis.

Figure 4

Noradrenergic modulation of evoked activity in BLA neurons is altered after seven and fourteen days of chronic cold exposure. A) Electrophysiological trace of a BLA neuron displaying an excitatory, orthodromic spike in response to entorhinal cortical stimulation. B) In control rats (dotted line), BLA activity evoked by stimulation of entorhinal cortex was significantly decreased during microiontophoresis of NE. In rats exposed to 7 or 14 days of cold, the inhibitory actions of NE were lessened (7 days, dashed line) and abolished (14 days, solid line). C) Electrophysiological trace of a BLA neuron displaying an excitatory, orthodromic spike in response to sensory association cortical stimulation. D) In control rats (dotted line), BLA activity evoked by stimulation of sensory association cortex was significantly decreased during microiontophoresis of NE. In rats exposed to 7 or 14 days of cold, the inhibitory actions of NE on evoked activity were lessened (14 days, solid line) and abolished (7 days, dashed line). E) Chronic cold exposure decreased the magnitude of NE-induced inhibition of Te3 and EC-evoked activity after 14 days of exposure, but not 7 days. F) Chronic cold exposure decreased the proportion of neurons that showed NE-induced inhibition of Te3 and EC-evoked activity after seven (gray bars) or 14 (white bars) of activity.