Questions about STDP as a General Model of Synaptic Plasticity

According to spike-timing-dependent plasticity (STDP), the timing of the Na+ spike relative to the EPSP determines whether LTP or LTD will occur. Here, we review our reservations about STDP. Most investigations of this process have been done under conditions in which the spike is evoked by postsynaptic current injection. Under more realistic conditions, in which the spike is evoked by the EPSP, the results do not generally support STDP. For instance, low-frequency stimulation of a group of synapses can cause LTD, not the LTP predicted by the pre-before-post sequence in STDP; this is true regardless of whether or not the EPSP is large enough to produce a Na+ spike. With stronger or more frequent stimulation, LTP can be induced by the same pre-before-post timing, but in this case block of Na+ spikes does not necessarily prevent LTP induction. Thus, Na+ spikes may facilitate LTP and/or LTD under some conditions, but they are not necessary, a finding consistent with their small size relative to the EPSP in many parts of pyramidal cell dendrites. The nature of the dendritic depolarizing events that control bidirectional plasticity is of central importance to understanding neural function. There are several candidates, including backpropagating action potentials, but also dendritic Ca2+ spikes, the AMPA receptor-mediated EPSP, and NMDA receptor-mediated EPSPs or spikes. These often appear to be more important than the Na+ spike in providing the depolarization necessary for plasticity. We thus feel that it is premature to accept STDP-like processes as the major determinant of LTP/LTD

Hippocampal and thalamic afferents form distinct synaptic microcircuits in the mouse infralimbic frontal cortex.

The selection of goal-directed behaviors is supported by neural circuits located within the frontal cortex. Frontal cortical afferents arise from multiple brain areas, yet the cell-type-specific targeting of these inputs is unclear. Here, we use monosynaptic retrograde rabies mapping to examine the distribution of afferent neurons targeting distinct classes of local inhibitory interneurons and excitatory projection neurons in mouse infralimbic frontal cortex. Interneurons expressing parvalbumin, somatostatin, or vasoactive intestinal peptide receive a large proportion of inputs from the hippocampus, while interneurons expressing neuron-derived neurotrophic factor receive a large proportion of inputs from thalamic regions. A similar dichotomy is present among the four different excitatory projection neurons. These results show a prominent bias among long-range hippocampal and thalamic afferent systems in their targeting to specific sets of frontal cortical neurons. Moreover, they suggest the presence of two distinct local microcircuits that control how different inputs govern frontal cortical information processing

Organizing memories for generalization in complementary learning systems

Memorization and generalization are complementary cognitive processes that jointly promote adaptive behavior. For example, animals should memorize safe routes to specific water sources and generalize from these memories to discover environmental features that predict new ones. These functions depend on systems consolidation mechanisms that construct neocortical memory traces from hippocampal precursors, but why systems consolidation only applies to a subset of hippocampal memories is unclear. Here we introduce a new neural network formalization of systems consolidation that reveals an overlooked tension—unregulated neocortical memory transfer can cause overfitting and harm generalization in an unpredictable world. We resolve this tension by postulating that memories only consolidate when it aids generalization. This framework accounts for partial hippocampal–cortical memory transfer and provides a normative principle for reconceptualizing numerous observations in the field. Generalization-optimized systems consolidation thus provides new insight into how adaptive behavior benefits from complementary learning systems specialized for memorization and generalization

Output-Mode Transitions Are Controlled by Prolonged Inactivation of Sodium Channels in Pyramidal Neurons of Subiculum

Transitions between different behavioral states, such as sleep or wakefulness, quiescence or attentiveness, occur in part through transitions from action potential bursting to single spiking. Cortical activity, for example, is determined in large part by the spike output mode from the thalamus, which is controlled by the gating of low-voltage–activated calcium channels. In the subiculum—the major output of the hippocampus—transitions occur from bursting in the delta-frequency band to single spiking in the theta-frequency band. We show here that these transitions are influenced strongly by the inactivation kinetics of voltage-gated sodium channels. Prolonged inactivation of sodium channels is responsible for an activity-dependent switch from bursting to single spiking, constituting a novel mechanism through which network dynamics are controlled by ion channel gating

Effects of Active Conductance Distribution over Dendrites on the Synaptic Integration in an Identified Nonspiking Interneuron

The synaptic integration in individual central neuron is critically affected by how active conductances are distributed over dendrites. It has been well known that the dendrites of central neurons are richly endowed with voltage- and ligand-regulated ion conductances. Nonspiking interneurons (NSIs), almost exclusively characteristic to arthropod central nervous systems, do not generate action potentials and hence lack voltage-regulated sodium channels, yet having a variety of voltage-regulated potassium conductances on their dendritic membrane including the one similar to the delayed-rectifier type potassium conductance. It remains unknown, however, how the active conductances are distributed over dendrites and how the synaptic integration is affected by those conductances in NSIs and other invertebrate neurons where the cell body is not included in the signal pathway from input synapses to output sites. In the present study, we quantitatively investigated the functional significance of active conductance distribution pattern in the spatio-temporal spread of synaptic potentials over dendrites of an identified NSI in the crayfish central nervous system by computer simulation. We systematically changed the distribution pattern of active conductances in the neuron's multicompartment model and examined how the synaptic potential waveform was affected by each distribution pattern. It was revealed that specific patterns of nonuniform distribution of potassium conductances were consistent, while other patterns were not, with the waveform of compound synaptic potentials recorded physiologically in the major input-output pathway of the cell, suggesting that the possibility of nonuniform distribution of potassium conductances over the dendrite cannot be excluded as well as the possibility of uniform distribution. Local synaptic circuits involving input and output synapses on the same branch or on the same side were found to be potentially affected under the condition of nonuniform distribution while operation of the major input-output pathway from the soma side to the one on the opposite side remained the same under both conditions of uniform and nonuniform distribution of potassium conductances over the NSI dendrite

Desynchronization of Neocortical Networks by Asynchronous Release of GABA at Autaptic and Synaptic Contacts from Fast-Spiking Interneurons

An activity-dependent long-lasting asynchronous release of GABA from identified fast-spiking inhibitory neurons in the neocortex can impair the reliability and temporal precision of activity in a cortical network

Axonal Gap Junctions Send Ripples through the Hippocampus

AbstractIn a paper by Schmitz and colleagues in this issue of Neuron, new evidence for the existence of gap junctions between pyramidal cell axons uncovers a mechanism for fast neural communication in the hippocampus. Electrical coupling between axons may be crucial during fast oscillations, which have been proposed to mediate memory consolidation