Interaction between Long-Term Potentiation and Depression in CA1 Synapses: Temporal Constrains, Functional Compartmentalization and Protein Synthesis

Abstract

Information arriving at a neuron via anatomically defined pathways undergoes spatial and temporal encoding. A proposed mechanism by which temporally and spatially segregated information is encoded at the cellular level is based on the interactive properties of synapses located within and across functional dendritic compartments. We examined cooperative and interfering interactions between long-term synaptic potentiation (LTP) and depression (LTD), two forms of synaptic plasticity thought to be key in the encoding of information in the brain. Two approaches were used in CA1 pyramidal neurons of the mouse hippocampus: (1) induction of LTP and LTD in two separate synaptic pathways within the same apical dendritic compartment and across the basal and apical dendritic compartments; (2) induction of LTP and LTD separated by various time intervals (0–90 min). Expression of LTP/LTD interactions was spatially and temporally regulated. While they were largely restricted within the same dendritic compartment (compartmentalized), the nature of the interaction (cooperation or interference) depended on the time interval between inductions. New protein synthesis was found to regulate the expression of the LTP/LTD interference. We speculate that mechanisms for compartmentalization and protein synthesis confer the spatial and temporal modulation by which neurons encode multiplex information in plastic synapses.

Persistent modifications of hippocampal synaptic function during remote spatial memory

“…In addition, there was no change observed in the depolarization envelope during synaptic plasticity (potentiation or depression) induction (Figure 6C). These observations suggest that long-term memory storage actively modulates the effective range of synaptic weights to frame incoming synaptic activity and regulate the subsequent processing of information (Pavlowsky and Alarcon, 2012; Park et al, 2015). …”

“…The manifold of findings indicate that long-term memory storage is not passive; rather, it appears to actively condition the effective range of synaptic weights to frame subsequent incoming synaptic activity and regulate the subsequent processing of information (Pavlowsky and Alarcon, 2012; Bannerman et al, 2014; Park et al, 2015). …”

Mechanisms of heterosynaptic metaplasticity

“…Although capture between basal and apical dendritic compartments can occur, it happens under limited conditions [27][28][29][30]. Instead STC interactions are more usually confined to specific dendritic compartments.…”

“…Interestingly, negative interactions that impair plasticity duration can also arise, particularly through competition for newly synthesized proteins. This occurs either when protein synthesis is limited or when strong induction protocols are used [30,34]. This competitive mechanism may represent an important brake on the extent to which STC mechanisms can enhance LTP, helping to avoid some of the positive-feedback instability on synaptic efficacy that the sliding threshold feature of the BCM theory was also designed to avoid.…”

Tools, methods, and applications for optophysiology in neuroscience

“…Electrophysiology is the prevalent approach to measuring and manipulating neuronal activity in experiments such as cellular stimulation combined with field recordings for functional analysis of specific brain regions (Salah and Perkins, 2011), inducing long-term potentiation and depression of neuronal activity (Pavlowsky and Alarcon, 2012), and observing sensory encoding of physiologically relevant stimuli (Trapani et al, 2009). Electrophysiological experiments can combine data from multiple electrodes (Xu et al, 2012), can integrate electrodes into a neuronal culture to facilitate prolonged measurements (Regehr et al, 1989), and can even combine simultaneous electrophysiology with optophysiology (Bender and Trussell, 2009).…”