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Histaminergic modulation of excitatory synaptic transmission in the rat basolateral amygdala
1Neuroscience Program, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Insights
Histamine has dual effects on excitatory synaptic transmission in the basolateral amygdala (BLA). It can suppress or potentiate these signals, influencing neuronal activity and potentially impacting emotional processing and disorders.
Area of Science:
- Neuroscience
- Neuropharmacology
- Synaptic Transmission
Background:
- Histamine is a neurotransmitter involved in various brain functions.
- The basolateral amygdala (BLA) plays a crucial role in emotional processing, learning, and memory.
- The precise role of histamine in modulating synaptic transmission within the BLA remains to be fully elucidated.
Purpose of the Study:
- To investigate the effects of histamine on excitatory synaptic transmission in the rat BLA.
- To determine the receptor mechanisms underlying histamine's actions in the BLA.
- To explore the potential implications of these modulatory effects in amygdala-related functions and disorders.
Main Methods:
- Intracellular and field potential recordings were performed in rat amygdala slices.
- Histamine and its receptor agonists/antagonists were applied to study synaptic responses.
- Paired-pulse facilitation was analyzed to infer presynaptic or postsynaptic mechanisms.
Main Results:
- Histamine exhibited dual effects: suppression (via presynaptic H3 receptors) and potentiation (via a novel, high-affinity postsynaptic mechanism).
- Suppression was associated with increased paired-pulse facilitation, indicating presynaptic action.
- Potentiation occurred at lower histamine concentrations and was independent of H1, H2, or H3 receptors.
Conclusions:
- Histamine differentially modulates excitatory synaptic transmission in the BLA through distinct receptor pathways.
- Presynaptic H3 receptors mediate histamine-induced suppression, while a postsynaptic mechanism underlies potentiation.
- These findings suggest histamine's significant role in regulating BLA neuronal activity, impacting emotional states and neurological conditions.
Abstract:
The effects of histamine on excitatory synaptic transmission between the external capsule and basolateral amygdala (BLA) were examined using intracellular and field potential recordings in rat amygdala slices. Bath application of histamine (20 microM) suppressed intracellular excitatory postsynaptic potentials (EPSPs; 70.3+/-5.1% of control amplitude) in 43 of 64 BLA neurons, and potentiated EPSPs (341+/-81% of control amplitude) in 21 neurons, without changing resting membrane potential or input resistance. The histamine-induced suppression of EPSPs was accompanied by an increase in paired-pulse facilitation of the slopes of EPSPs, suggesting a presynaptic locus of the action. The suppressive effect could be blocked by the selective H3 antagonist thioperamide, and mimicked by the selective H3 agonist R-alpha-methylhistamine, indicating that the suppressive effect is mediated by the presynaptic H3 receptor. The potentiating effect of histamine on EPSPs was not accompanied by the change of paired-pulse facilitation and was not affected by the presence of H1, H2 or H3 receptor antagonists. In addition, the effective concentration of agonist to produce 50% of maximal response (EC50) of the potentiating action of histamine is 49 nM, much lower than the EC50 (470 nM) of the H3 receptor-mediated suppressive effect characterized here. These observations suggest a novel, high affinity and postsynaptically mediated effect of histamine. In extracellular recordings, histamine, at low concentration (200 nM), consistently potentiated field potentials. At high concentration (20 microM), histamine suppressed field potentials, but potentiated field potentials when H3 receptors were blocked. Taken together, these results revealed that histamine, via the presynaptic H3 receptor and a currently unknown mechanism, decreases or increases excitatory synaptic transmission in the BLA respectively. This specific histaminergic modulation of neuronal activity in the amygdala may play an important role in amygdala-mediated physiological and pathophysiological processes, such as fear, emotional learning and memory, temporal lobe epilepsy, and affective disorders.
