Myenteric neurons of the mouse small intestine undergo significant electrophysiological and morphological changes during postnatal development

Abstract

Key points• Different functional types of neurons within the gut wall form circuits that regulate intestinal motility.• To examine the postnatal development of electrical properties of different classes of enteric neurons, we performed intracellular recordings from neurons in the mouse duodenum at three ages: postnatal day (P)0, P10-11 and adult.• Like adults, two main morphological classes of neurons are present at P0 and P10-11. P0and P10-11 neurons with Dogiel type II (DII) morphology had multiple long processes that achieved their adult projection length by P10-11. However, they differed electrophysiologically from adult DII neurons in that they displayed prominent afterdepolarizing potentials.• Most electrical properties of neurons with a single long process were mature by P10-11.However, these neurons showed significant postnatal changes in morphology and projection length.• Major morphological and electrophysiological changes in enteric neurons occur postnatally, which could underlie changes in gut motility during development.Abstract Organized motility patterns in the gut depend on circuitry within the enteric nervous system (ENS), but little is known about the development of electrophysiological properties and synapses within the ENS. We examined the electrophysiology and morphology of myenteric neurons in the mouse duodenum at three developmental stages: postnatal day (P)0, P10-11, and adult. Like adults, two main classes of neurons could be identified at P0 and P10-11 based on morphology: neurons with multiple long processes that projected circumferentially (Dogiel type II morphology) and neurons with a single long process. However, postnatal Dogiel type II neurons differed in several electrophysiological properties from adult Dogiel type II neurons. P0 and P10-11 Dogiel type II neurons exhibited very prominent Ca 2+ -mediated afterdepolarizing potentials (ADPs) following action potentials compared to adult neurons. Adult Dogiel type II neurons are characterized by the presence of a prolonged afterhyperpolarizing potential (AHP), but AHPs were very rarely observed at P0. The projection lengths of the long processes of Dogiel type II neurons were mature by P10-11. Uniaxonal neurons in adults typically have fast excitatory postsynaptic potentials (fEPSPs, 'S-type' electrophysiology) mainly mediated by nicotinic receptors. Nicotinic-fEPSPs were also recorded from neurons with a single long process at P0 and P10-11. However, these neurons underwent major developmental changes in morphology, from predominantly filamentous neurites at birth to lamellar dendrites in mature mice. Unlike Dogiel type II neurons, the projection lengths of neurons with a single long process matured after P10-11. Slow EPSPs were rarely observed in P0/P10-11 neurons. This work shows that, although functional synapses are present and two classes of neurons can be distinguished electrophysiologically and morphologically at P0, major changes in electrophysiological properties and morphology occur during the postnatal development of th...

Transplanted progenitors generate functional enteric neurons in the postnatal colon

“…The durations and amplitudes of evoked fEPSPs and the number of fEPSPs in groups elicited by single-pulse stimulations were also reduced by hexamethonium (data not shown). The resting membrane potential and input resistance of graft-derived neurons (Table 1) were similar to those recently reported for P0 and P10 enteric neurons (52), but the neurons were more depolarized than adult enteric neurons (53).…”

Building a second brain in the bowel

“…Although both DG I and DG II neurons are present by P0 in mice, most DG I neurons possess filamentous instead of lamellar dendritic projections. The proportion of neurons with lamellar dendrites increases until adulthood (117). Furthermore, while the length of DG II circumferential projections remains constant despite dramatic increases in bowel circumference from P0 to adulthood, DG I longitudinal axons continue to grow, though more slowly than does the bowel.…”

Morphological, immunocytochemical, and functional characterization of esophageal enteric neurons in primary culture

“…1A, inset). One type of neuron is monoaxonal and has short club-like dendrites, which resembles Dogiel type I as described in in situ ex vivo whole wall preparations (6,7,16,37). On the other hand, another type of neuron that is larger than most other neurons has smooth cell bodies with multiple long processes.…”

“…Because we used enzymes and other processes to isolate neurons from the gastrointestinal tract and primary cultured them, their morphological appearance may not necessarily be the same as the ones in situ. However, we are certain of our ability to obtain primary culture of the esophageal enteric neurons with morphological appearance that resembles the intestinal enteric neurons published in the literature (6,7,16,37).…”

“…Morphological appearance is one of the identifying features of neurons in both the central nervous system and ENS (16,19). The shape of neurons does not vary across species even with different sizes of animals (6, 7).…”