Possible novel features of synaptic regulation during long-term facilitation in Aplysia

Most studies of molecular mechanisms of synaptic plasticity have focused on the sequence of changes either at individual synapses or in the cell nucleus. However, studies of long-term facilitation at Aplysia sensory neuron–motor neuron synapses in isolated cell culture suggest two additional features of facilitation. First, that there is also regulation of the number of synaptic contacts between two neurons, which may occur at the level of cell pair-specific branch points in the neuronal arbor. Branch points contain many molecules that are involved in protein synthesis-dependent long-term facilitation including neurotrophins and the RNA binding protein CPEB. Second, the regulation involves homeostatic feedback and tends to keep the total number of contacts between two neurons at a fairly constant level both at rest and following facilitation. That raises the question of how facilitation and homeostasis can coexist. A possible answer is suggested by the findings that they both involve spontaneous transmission and postsynaptic Ca²⁺, which can have bidirectional effects similar to LTP and LTD in hippocampus. In addition, long-term facilitation can involve a change in the set point of homeostasis, which could be encoded by plasticity molecules such as CPEB and/or PKM. A computational model based on these ideas can qualitatively simulate the basic features of both facilitation and homeostasis of the number of contacts.

Synaptic plasticity is a change in strength of the synaptic connection (postsynaptic potential or PSP) between neurons and includes increases during facilitation and decreases during depression. Plasticity is thought to underlie circuit formation during development and learning and memory in adults, and correspondingly to be defective in neurodevelopmental disorders including autism, ADHD, and schizophrenia as well as learning and memory disorders including Alzheimer''s, age-related memory loss, and drug addiction (Hawkins 2013; Hawkins et al. 2017). Most studies of molecular mechanisms of synaptic plasticity have focused on either changes at individual synapses or gene regulation in the cell nucleus. However, studies of long-term facilitation at Aplysia sensory neuron–motor neuron (SN–MN) synapses in isolated cell culture (Glanzman et al. 1990), sensitization in the intact animal (Wainwright et al. 2004), and long-term potentiation in hippocampal neurons (Antonova et al. 2001, 2009) have shown that there are also changes in the number of contacts between presynaptic varicosities and the postsynaptic neuron. We refer to these as synaptic contacts although not all of them are functional synapses (Kim et al. 2003). The number of contacts is thought to be an important determinant of the strength of the PSP (Zhang et al. 2003) and to be different for different neuron pairs. It also increases during long-term facilitation of the PSP and is thought to be a major determinant of the time course of the facilitation (Bailey and Chen 1989).As in other systems (Antonova et al. 2001, 2009; Holtmaat and Svoboda 2009), the contacts are dynamic and are continually being formed and eliminated, but the total number and the PSP remain fairly constant both at rest and during long-term facilitation (Miniaci et al. 2008; Chen et al. 2014). Furthermore, the number of contacts and the PSP return to baseline when maintenance of the facilitation is blocked, but the individual contacts are not all the same as they were before facilitation. These results have led some to suggest that memories are not stored at individual synaptic contacts, as is often supposed, but rather are stored in the nucleus (Chen et al. 2014). However, most of the previous experiments have involved a single SN and a single MN, so it has not been possible to examine the synapse specificity of the effects. Experiments with one SN and two MNs (Martin et al. 1997) or two SNs and 1 MN (Schacher et al. 1997) have shown that facilitation of the number of synaptic contacts and the PSP is specific to the stimulated synaptic pair (e.g., SN–MN1) and does not occur for the other pair (e.g., SN–MN2). These results should generalize to multiple pre- and postsynaptic partners and suggest two novel features of synaptic regulation during plasticity: (1) that the number of synaptic contacts between two neurons is regulated, and (2) that the regulation is homeostatic. We first describe those features and some of the evidence supporting them, then propose a model that could account for them and present computational modeling to illustrate the plausibility of the model.     

Multi-target visual search organisation across the lifespan: cancellation task performance in a large and demographically stratified sample of healthy adults

Accurate tests of cognition are vital in (neuro)psychology. Cancellation tasks are popular tests of attention and executive function, in which participants find and ‘cancel’ targets among distractors. Despite extensive use in neurological patients, it remains unclear whether demographic variables (that vary among patients) affect cancellation performance. Here, we describe performance in 523 healthy participants of a web-based cancellation task. Age, sex, and level of education did not affect cancellation performance in this sample. We provide norm scores for indices of spatial bias, perseverations, revisits, processing speed, and search organisation. Furthermore, a cluster analysis identified four cognitive profiles among participants, characterised by many omissions (N=18), many revisits (N=18), relatively poor search organisation (N=125), and relatively good search organisation (N=362). Thus, patient scores pertaining to search organisation should be interpreted cautiously: Given the large proportion of healthy individuals with poor search organisation, disorganised search in patients might be pre-existing rather than disorder-related.     

Automatic behavioural responses to valence: Evidence that facial action is facilitated by evaluative processing

Are motor schemata of facial action spontaneously activated upon the processing of evaluative information? In this case, the processing of positive evaluative information should immediately trigger the motor schema of smiling, and the processing of negative information should trigger frowning. This hypothesis was tested in two experiments in which participants were required to respond to positive and negative words by either smiling or frowning. Electromyogram (EMG) activity was recorded over the brow muscle region (corrugator supercilii) and over the cheek muscle region (zygomaticus major) in order to quantify the latency of muscular response as a dependent measure. In Experiment 1 we found that participants were faster at contracting their zygomaticus muscle (which is involved in smiling) when evaluating positive words, and faster at contracting their corrugator muscle (which is involved in frowning) when evaluating negative words. In Experiment 2, participants were required to respond with the contraction of one of the two muscles whenever a word appeared on the computer screen. Again, we found that responses were faster to congruent response valence combinations than to incongruent response valence combinations. These findings support the hypothesis that evaluative processing is directly linked to motor schemata of facial muscles.