Postnatal development of electrophysiological properties of principal neurons in the rat basolateral amygdala

Abstract

Key points• The amygdala mediates emotional processing, in particular fear learning, and disruption of its function is thought to contribute to the developmental origins of psychiatric disorders like depression, anxiety and autism spectrum disorders.• It is difficult to identify the causes of these disorders or provide effective intervention because most of what is known of amygdala physiology is based on the adult.• Using the whole-cell patch clamp technique, we show that neurons in the developing rat amygdala undergo drastic changes to their electrophysiology, including passive membrane properties, intrinsic currents and resonance.• This provides the first evidence that amygdala neuron physiology is dynamic before adulthood, and likely to contribute to emotional development.• The results help us better understand the normative development of emotional processing and identify critical periods of maturation that may be sensitive to insult.Abstract The basolateral amygdala (BLA) is critically involved in the pathophysiology of psychiatric disorders, which often emerge during brain development. Several studies have characterized postnatal changes to the morphology and biochemistry of BLA neurons, and many more have identified sensitive periods of emotional maturation. However, it is impossible to determine how BLA development contributes to emotional development or the aetiology of psychiatric disorders because no study has characterized the physiological maturation of BLA neurons. We addressed this critical knowledge gap for the first time using whole-cell patch clamp recording in rat BLA principal neurons to measure electrophysiological properties at postnatal day (P)7, P10, P14, P21, P28 and after P35. We show that intrinsic properties of these neurons undergo significant transitions before P21 and reach maturity around P28. Specifically, we observed significant reductions in input resistance and membrane time constant of nearly 10-and 4-fold, respectively, from P7 to P28. The frequency selectivity of these neurons to input also changed significantly, with peak resonance frequency increasing from 1.0 Hz at P7 to 5.7 Hz at P28. In the same period, maximal firing frequency significantly increased and doublets and triplets of action potentials emerged. Concomitantly, individual action potentials became significantly faster, firing threshold hyperpolarized 6.7 mV, the medium AHP became faster and shallower, and a fast AHP emerged. These results demonstrate neurons of the BLA undergo vast change D. E. Ehrlich and S. J. Ryan contributed equally to this work.

The Neuro-Environmental Loop of Plasticity: A Cross-Species Analysis of Parental Effects on Emotion Circuitry Development Following Typical and Adverse Caregiving

“…This sensitive period appears to coincide with a stage of considerable amygdala maturation (see, eg, Ehrlich et al, 2012Ehrlich et al, , 2013, fitting with the idea that periods of rapid growth open up opportunities for environmental input into system functioning and development (Lupien et al, 2009). Importantly, the termination of this sensitive period appears to coincide not only with increased age-associated neural maturation but also with the increased independence from parents as individuals approach adolescence.…”

“…Amygdala physiology also undergoes significant change early in life. Animal studies have demonstrated continued maturation of the intrinsic properties of amygdala principal neurons (eg, increases in maximal firing and peak resonance frequency; Ehrlich et al, 2012), and of inhibitory neurotransmitter systems within the amygdala (ie, γ-aminobutyric acid (GABA); Ehrlich et al, 2013) until early adolescence. In terms of functionality, the amygdala exhibits very robust responding to emotional events in childhood, with amygdala reactivity to emotional stimuli then decreasing across adolescence and into adulthood (Decety et al, 2012;Gee et al, 2013b;Tottenham, 2012;Vink et al, 2014); however, see Moore et al (2012) and Hare et al (2008) for a slightly different outcome.…”

Effects of Repeated Stress on Age-Dependent GABAergic Regulation of the Lateral Nucleus of the Amygdala

“…It is unclear why blockade of GABA receptors does not cause an increase in the number of active LAT neurons in adult rats (although there is a trend in this direction). Possible explanations may include additional sources of regulation (eg greater contribution of h channels, SK channels, GABA b receptors; Ehrlich et al, 2012;Bosch and Ehrlich, 2015) that suppress neuron firing even when GABA A receptors are blocked.…”

Prenatal stress, regardless of concurrent escitalopram treatment, alters behavior and amygdala gene expression of adolescent female rats

“…The concentration gradient of chloride across neuronal membranes, which dictates the strength and sign of GABAergic synaptic currents, is established by chloride transporters that accumulate or extrude chloride ions. During postnatal development, BLA neurophysiology is highly dynamic (Ehrlich et al, 2012; Thompson et al, 2008), as neurons reduce expression of the chloride accumulator, NKCC1 (Na-K-Cl cotransporter 1), in favor of the chloride extruder, KCC2 (K-Cl cotransporter 2), switching GABA A receptors from excitatory to inhibitory (Ehrlich et al, 2013). In adults, stress influences GABAergic transmission by regulating the balance NKCC1 and KCC2 expression (Maguire, 2014; Sarkar et al, 2011).…”