Developmental Regulation of Membrane Potential Oscillations inthe Basolateral Amygdala: Modulation by Beta-Adrenergic ReceptorActivation Open Access
Ryan, Steven John (2015)
Abstract
The basolateral nucleus of the amygdala (BLA) is a brain region of fundamental importance in enabling emotional memory. A wealth of evidence also demonstrates the causative role that dysfunction of the BLA can play in many psychiatric disorders, which often emerge during juvenile and adolescent brain development. In order to effectively treat these disorders, interventions must be developed that are appropriate to the age of diagnosis. The existing literature demonstrates a large number of BLA-dependent behaviors mature during juvenile development, which suggests there must be massive concomitant changes to how the BLA processes information. Despite the apparent importance and dynamic nature of BLA development, however, almost nothing is known about the normative development of the juvenile BLA. In this dissertation, we begin to address this knowledge gap by performing an extensive characterization of the physiology and morphology of developing BLA principal neurons with the ultimate goal of identifying putative critical periods which may exhibit particular sensitivity to disruption or opportunity for intervention. In adult rats, synchronized neural activity in the BLA and related regions is critical for emotional memory formation. Little was known, however, about the cellular mechanisms contributing to synchronization in the BLA, or if a similar process was utilized across development to regulate affective behavior. Toward this end, we first explore low-frequency membrane potential oscillations and synchronous synaptic activity in adult rats. We were able to evoke low-frequency MPOs in BLA principal neurons and provide evidence suggesting that these oscillations serve to synchronize the activity of large ensembles of neurons. We also show that these MPOs are subject to modulation by intracellular signaling cascade which is itself regulated by the activity of neuromodulators. These results motivated us to explore the development of this critical facet of BLA physiology. However, in order to effectively do so, we needed to characterize more fundamental aspects of the development of BLA principal neurons. Thus, we next characterized the intrinsic physiology and dendritic morphology of these neurons. These studies showed dramatic maturation of the BLA across the first postnatal month: neuronal input resistance drops by nearly 10-fold, intrinsic voltage-gated currents mature substantially, and aggregate dendritic length increases by nearly 4-fold. Many other dramatic changes unfold over this same period, which we discuss in detail below. Finally, catecholaminergic innervation of the BLA shows major changes over this same time period, and we further demonstrated a developmental progression in the ability of norepinephrine to enhance tuned, frequency-specific MPOs and to facilitate organized firing activity by synchronous synaptic activity. These studies will provide an important context for future work looking at the development of psychiatric disorders in the juvenile brain.
Table of Contents
Chapter 1 - General Introduction. 1
Chapter 2 - Spike-Timing Precision and Neuronal Synchrony are Enhanced by an Interaction between Synaptic Inhibition and Membrane Oscillations in the Amygdala. 5
Abstract. 5
Introduction. 7
Materials and Methods. 9
Results. 14
Discussion. 33
Synchronized inhibition drives coordinated activity of BLA principal neurons. 33
Resonance frequency and intrinsic membrane oscillations in BLA principal neurons. 36
Implications for learning and memory. 39
Chapter 3 - Postnatal Development of Electrophysiological Properties of Principal Neurons in the Rat Basolateral Amygdal. 44
Abstract. 44
Introduction. 45
Materials and Methods. 47
Results. 53
Discussion. 72
Maturation of passive membrane properties.73
Maturation of membrane potential oscillations and resonance. 73
Maturation of Ih and its contribution to resonance. 75
Maturation of trains of action potentials. 77
Maturation of action potentials and AHPs. 79
Maturation of amygdala morphology and connectivity. 80
Chapter 4 - Morphology of Developing Principal Neurons in the Rat Basolateral Amygdala. 83
Abstract. 83
Introduction. 85
Materials and Methods. 86
Results. 9 3
Discussion. 105
Somatic Development. 105
Dendritic Morphology. 107
Dendritic spine emergence. 110
Chapter 5 - Postnatal Development of Spike-Timing Precision and Membrane Potential Oscillations in Principal Neurons of the Rat Basolateral Amygdal. 113
Introduction. 114
Materials and Methods. 115
Results. 120
Discussion. 130
Compound IPSPs can enhance spike-timing precision throughout juvenile development. 131
MPOs are modulated by β adrenoceptors throughout juvenile development. 132
Chapter 6 - Summary & Future Directions. 134
About this Dissertation
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