Anxiogenic modulation of spontaneous and evoked neuronal activity in the basolateral amygdala

Abstract

The amygdala has a well-established role in stress, anxiety, and aversive learning, and anxiolytic and anxiogenic agents are thought to exert their behavioral actions via the amygdala. However, despite extensive behavioral data, the effects of noradrenergic anxiogenic drugs on neuronal activity within the amygdala have not been examined. The present experiments examined how administration of the anxiogenic drug yohimbine affects spontaneous and evoked neuronal activity in the basolateral amygdala (BLA) of rats. Yohimbine produced both excitatory and inhibitory effects on neurons of the BLA, with an increase in spontaneous activity being the predominant response in the lateral and basomedial nuclei of the BLA. Furthermore, yohimbine tended to facilitate neuronal responses evoked by electrical stimulation of the entorhinal cortex, with this facilitation seen more often in lateral and basomedial nuclei of the BLA. These data are the first to examine the effects of the anxiogenic agent yohimbine on BLA neuronal activity, and suggest that neurons in specific subnuclei of the amygdala exhibit unique responses to administration of such pharmacological agents.

Figure 1. Neuronal subtypes examined in this study

A) Neurons were identified as projection neurons via antidromic activation, and classified as projection neurons, interneurons, or “unclassified,” based on firing rate and action potential duration. Neurons with longer duration action potentials had lower firing rates and were operationally defined as projection neurons (diamonds) some of which demonstrated antidromic activation from terminal sites (filled diamonds). Neurons with shorter duration action potentials had higher firing rates and were operationally defined as interneurons (open circles). B) Trace of a neuron antidromically activated (asterisk) by stimulation of entorhinal cortex (arrow). C) Latency distribution for the neuron displayed in B. Note the constant spike latency evoked by EC stimulation.

Figure 1. Neuronal subtypes examined in this study

A) Neurons were identified as projection neurons via antidromic activation, and classified as projection neurons, interneurons, or “unclassified,” based on firing rate and action potential duration. Neurons with longer duration action potentials had lower firing rates and were operationally defined as projection neurons (diamonds) some of which demonstrated antidromic activation from terminal sites (filled diamonds). Neurons with shorter duration action potentials had higher firing rates and were operationally defined as interneurons (open circles). B) Trace of a neuron antidromically activated (asterisk) by stimulation of entorhinal cortex (arrow). C) Latency distribution for the neuron displayed in B. Note the constant spike latency evoked by EC stimulation.

Figure 1. Neuronal subtypes examined in this study

A) Neurons were identified as projection neurons via antidromic activation, and classified as projection neurons, interneurons, or “unclassified,” based on firing rate and action potential duration. Neurons with longer duration action potentials had lower firing rates and were operationally defined as projection neurons (diamonds) some of which demonstrated antidromic activation from terminal sites (filled diamonds). Neurons with shorter duration action potentials had higher firing rates and were operationally defined as interneurons (open circles). B) Trace of a neuron antidromically activated (asterisk) by stimulation of entorhinal cortex (arrow). C) Latency distribution for the neuron displayed in B. Note the constant spike latency evoked by EC stimulation.

Figure 2. Yohimbine administration caused a two-fold increase in norepinephrine levels in the BLA

Yohimbine (0.5mg/kg, i.v, arrow) caused a rapid rise in NE levels measured by a microdialysis probe placed into the BLA (*p<0.05 compared to baseline).

Figure 3. Effects of yohimbine on BLA neuron activity

A) Yohimbine causes both excitation and inhibition of neuronal firing in the BLA. B) Projection neurons were more often excited than inhibited following yohimbine administration, whereas an equal number of interneurons exhibited excitation and inhibition. C)When examined based on neuron location, neurons in the BLA show approximately equal numbers of neurons that were excited and inhibited, whereas a greater proportion of lateral and basomedial neurons showed excitation in response to yohimbine (ALL=all neurons, BL=basolateral nucleus, LAT=lateral nucleus, BM=basomedial nucleus).

Figure 3. Effects of yohimbine on BLA neuron activity

A) Yohimbine causes both excitation and inhibition of neuronal firing in the BLA. B) Projection neurons were more often excited than inhibited following yohimbine administration, whereas an equal number of interneurons exhibited excitation and inhibition. C)When examined based on neuron location, neurons in the BLA show approximately equal numbers of neurons that were excited and inhibited, whereas a greater proportion of lateral and basomedial neurons showed excitation in response to yohimbine (ALL=all neurons, BL=basolateral nucleus, LAT=lateral nucleus, BM=basomedial nucleus).

Figure 3. Effects of yohimbine on BLA neuron activity

A) Yohimbine causes both excitation and inhibition of neuronal firing in the BLA. B) Projection neurons were more often excited than inhibited following yohimbine administration, whereas an equal number of interneurons exhibited excitation and inhibition. C)When examined based on neuron location, neurons in the BLA show approximately equal numbers of neurons that were excited and inhibited, whereas a greater proportion of lateral and basomedial neurons showed excitation in response to yohimbine (ALL=all neurons, BL=basolateral nucleus, LAT=lateral nucleus, BM=basomedial nucleus).

Figure 4. Effects of yohimbine on BLA neuronal activity evoked by stimulation of entorhinal cortex

A) Trace from a neuron that is activated orthodromically (asterisk) by stimulation of entorhinal cortex (arrow). B) Latency distribution for the neuron displayed in A. C). Yohimbine primarily significantly increased EC-evoked activity of neurons in the BLA (p=0.02 compared to control), but a subset of neurons exhibited a significant decrease in evoked activity (p=0.03 compared to control).

Figure 4. Effects of yohimbine on BLA neuronal activity evoked by stimulation of entorhinal cortex

A) Trace from a neuron that is activated orthodromically (asterisk) by stimulation of entorhinal cortex (arrow). B) Latency distribution for the neuron displayed in A. C). Yohimbine primarily significantly increased EC-evoked activity of neurons in the BLA (p=0.02 compared to control), but a subset of neurons exhibited a significant decrease in evoked activity (p=0.03 compared to control).

Figure 4. Effects of yohimbine on BLA neuronal activity evoked by stimulation of entorhinal cortex

A) Trace from a neuron that is activated orthodromically (asterisk) by stimulation of entorhinal cortex (arrow). B) Latency distribution for the neuron displayed in A. C). Yohimbine primarily significantly increased EC-evoked activity of neurons in the BLA (p=0.02 compared to control), but a subset of neurons exhibited a significant decrease in evoked activity (p=0.03 compared to control).

Figure 5. Effects of yohimbine on spontaneous and evoked BLA neuronal activity

There is no clear correlation between the effects of yohimbine on baseline firing and evoked activity. While a greater proportion of neurons displayed changes in evoked and spontaneous activity in the same direction (increase in both, or decrease in both), this was not significant.