Neurexins and Neuroligins: Recent Insights from Invertebrates

During brain development, each neuron must find and synapse with the correct pre- and postsynaptic partners. The complexity of these connections and the relatively large distances some neurons must send their axons to find the correct partners makes studying brain development one of the most challenging, and yet fascinating disciplines in biology. Furthermore, once the initial connections have been made, the neurons constantly remodel their dendritic and axonal arbours in response to changing demands. Neurexin and neuroligin are two cell adhesion molecules identified as important regulators of this process. The importance of these genes in the development and modulation of synaptic connectivity is emphasised by the observation that mutations in these genes in humans have been associated with cognitive disorders such as Autism spectrum disorders, Tourette syndrome and Schizophrenia. The present review will discuss recent advances in our understanding of the role of these genes in synaptic development and modulation, and in particular, we will focus on recent work in invertebrate models, and how these results relate to studies in mammals

Decreased Response to Acetylcholine during Aging of <i>Aplysia</i> Neuron R15

<div><p>How aging affects the communication between neurons is poorly understood. To address this question, we have studied the electrophysiological properties of identified neuron R15 of the marine mollusk <i>Aplysia californica</i>. R15 is a bursting neuron in the abdominal ganglia of the central nervous system and is implicated in reproduction, water balance, and heart function. Exposure to acetylcholine (ACh) causes an increase in R15 burst firing. Whole-cell recordings of R15 in the intact ganglia dissected from mature and old <i>Aplysia</i> showed specific changes in burst firing and properties of action potentials induced by ACh. We found that while there were no significant changes in resting membrane potential and latency in response to ACh, the burst number and burst duration is altered during aging. The action potential waveform analysis showed that unlike mature neurons, the duration of depolarization and the repolarization amplitude and duration did not change in old neurons in response to ACh. Furthermore, single neuron quantitative analysis of acetylcholine receptors (AChRs) suggested alteration of expression of specific AChRs in R15 neurons during aging. These results suggest a defect in cholinergic transmission during aging of the R15 neuron. </p> </div

Electrophysiological measurements in R15 neuron in the intact ganglia.

<p>A: Six types of bioelectric activity were recorded in R15 neurons. Percent R15 neurons with each activity are shown in bar graphs. Red bars: Mature; Black bars: Old. Numbers of neurons that showed specific activity is shown on each bar graph. B: Resting membrane potential of rhythmic bursting R15 from mature (bM-R15) and old (bO-R15) animals. Red: bM-R15 and black: bO-R15. Statistical analysis suggests that there are no significant differences (n=4; Student’s t test, p > 0.05) in resting membrane potentials of bM-R15 and bO-R15 neurons.</p

Analysis of action potential waveform in rhythmic bursting R15 from mature and old animals.

<p>A: action potentials in a single burst. B: measurements of waveform parameters (Depolarization amplitude, Depolarization Duration, Repolarization amplitude, Repolarization duration). Bar graphs showing the mean depolarization amplitude (C), the mean depolarization duration (D), repolarization amplitude (E), repolarization duration (F) of AP waveforms recorded in rhythmic R15 bursting neurons from old and mature animals, before and after 1 mM ACh application. Values are expressed as mean ± SEM. mV: milli volt; msec: milli seconds. An asterisk or a black-filled square indicates statistically significant differences. Differences were considered significant (n=4; One way ANOVA and Tukey’s HSD test) at the level of p <0.05 (asterisk) or p <0.01 (square). G & H: Representative action potentials waveforms of R15 bursting activity recorded in bM-R15 (G) and bO-R15 (H) neurons before and after 1 mM ACh application. bM-R15: rhythmic bursting R15 from mature animals; bO-R15: rhythmic bursting R15 from old animals, bM-R15 ACh and bO-R15 ACh are bM-R15 or bO-R15 neurons after ACh exposure.</p

Quantitative analysis of AChRs in single R15 neurons from mature and old animals.

<p>RNAs isolated from single R15 neurons were amplified and used for qPCR analysis. Data was normalized to 18S rRNA levels. Relative expression of five AChRs in old R15 neurons is shown in bar graphs. Fold change ± SEM are shown. One way ANOVA and Tukey’s HSD post hoc test was used to determine the statistical significance where **p value < 0.01, ***p value < 0.001.</p