NMDA receptors involvement in memory and prediction

Memory and prediction are fundamental cognitive functions shaping our
daily activities, with prediction enhancing the likelihood of successful
action and relying heavily on memory. Studies indicate that spike
timing-dependent plasticity (STDP), a mechanism altering synaptic weights
based on temporal coordination, is crucial for memory, with NMDA
activation playing a pivotal role. Our investigation aimed to assess the
impact of inhibiting NMDA activation on long-term memory and prediction in
random in-vitro networks of dissociated rat cortical neurons using MEAs.
During long-term memory formation, experiences are initially encoded in
the hippocampus and later reactivated, triggering neocortical areas in
systems consolidation. To study memory and prediction, we subjected
cultures to focal, low-frequency electrical stimulation. For memory, a 10
min stimulation with 1 h intervals of spontaneous activity was employed.
For prediction, 20 h focal stimulation with random interstimulus intervals
was applied. NMDA receptors were blocked with amino-5-phosphonovaleric
acid (APV). Long-term memory formation was assessed  estimating
functional connectivity with Conditional Firing Probabilities and possible
connectivity changes using Euclidean distances. In control cultures, focal
stimulation induced persistent connectivity changes, indicating memory
trace formation. APV treated cultures showed no connectivity changes.
Prediction and its relationship with memory were studied using mutual
information between activity and future (prediction) or past (short-term
memory) stimuli. Prediction occurred in both groups, but its dependence on
short-term memory decreased over time only in the control group when
long-term memory traces are formed. In conclusion, our findings suggest
that formation of long-term memory traces in random cortical networks
critically depends on NMDA activation. Additionally, if long-term memory
is impaired, prediction still requires short-term memory. Our in-vitro
model using MEAs provides a simulation of the long-term memory process and
prediction.