Spike timing-dependent plasticity of neural circuits

Recent findings of spike timing-dependent plasticity (STDP) have stimulated much interest among experimentalists and theorists. Beyond the traditional correlation-based Hebbian plasticity, STDP opens up new avenues for understanding information coding and circuit plasticity that depend on the precise timing of neuronal spikes. Here we summarize experimental characterization of STDP at various synapses, the underlying cellular mechanisms, and the associated changes in neuronal excitability and dendritic integration. We also describe STDP in the context of complex spike patterns and its dependence on the dendritic location of the synapse. Finally, we discuss timing-dependent modification of neuronal receptive fields and human visual perception and the computational significance of STDP as a synaptic learning rule.     

Spike timing improves olfactory capabilities in mammals

An issue that has puzzled neuroscientists for decades is what role, if any, temporal patterning of action potentials has in determining behavior. A study in this issue of Neuron by Cury and Uchida in the rat olfactory system provides evidence that such patterns could help mammals to identify and discriminate odors.     

Spike timing dependent synaptic plasticity in biological systems

 Association of a presynaptic spike with a postsynaptic spike can lead to changes in synaptic efficacy that are highly dependent on the relative timing of the pre- and postsynaptic spikes. Different synapses show varying forms of such spike-timing dependent learning rules. This review describes these different rules, the cellular mechanisms that may be responsible for them, and the computational consequences of these rules for information processing and storage in the nervous system. Received: 16 January 2002 / Accepted: 3 June 2002 Acknowledgements. This research is supported in part by a National Science Foundation grant IBN 98-08887 (awarded to PDR), and by National Institutes of Health grants R01-MH49792 (awarded to CCB), R01-MH60996 (awarded to CCB), and R01-MH60996 (awarded to PDR). Correspondence to: P. D. Roberts (e-mail: robertpa@ohsu.edu)     

Spike timing,calcium signals and synaptic plasticity

Plasticity at central synapses depends critically on the timing of presynaptic and postsynaptic action potentials. Key initial steps in synaptic plasticity involve the back-propagation of action potentials into the dendritic tree and calcium influx that depends nonlinearly on the action potential and synaptic input. These initial steps are now better understood. In addition, recent studies of processes as diverse as gene expression and channel inactivation suggest that responses to calcium transients depend not only their amplitude, but on their time course and on the location of their origin.     

Spike timing in the mammalian visual system.

Evidence is accumulating for the existence of mechanisms that create and detect synchrony among action potentials on short time scales both within and between neurons. Progress is most rapid in the retina, the lateral geniculate nucleus, and cortical slices, where signal flow is better understood or more manipulable. The debate over the functional relevance of spike timing in cortex has gained substance from new computational models but remains unresolved.     

Spike timing and visual processing in the retinogeniculocortical pathway

Although the visual response properties of neurons along the retinogeniculocortical pathway have been studied for decades, relatively few studies have examined how individual neurons along the pathway communicate with each other. Recent studies in the cat (Felis domestica) now show that the strength of these connections is very dynamic and spike timing plays an important part in determining whether action potentials will be transferred from pre- to postsynaptic cells. This review explores recent progress in our understanding of what role spike timing has in establishing different patterns of geniculate activity and how these patterns ultimately drive the cortex.     

Decision making in recurrent neuronal circuits

Decision making has recently emerged as a central theme in neurophysiological studies of cognition, and experimental and computational work has led to the proposal of a cortical circuit mechanism of elemental decision computations. This mechanism depends on slow recurrent synaptic excitation balanced by fast feedback inhibition, which not only instantiates attractor states for forming categorical choices but also long transients for gradually accumulating evidence in favor of or against alternative options. Such a circuit endowed with reward-dependent synaptic plasticity is able to produce adaptive choice behavior. While decision threshold is a core concept for reaction time tasks, it can be dissociated from a general decision rule. Moreover, perceptual decisions and value-based economic choices are described within a unified framework in which probabilistic choices result from irregular neuronal activity as well as iterative interactions of a decision maker with an uncertain environment or other unpredictable decision makers in a social group.     

Regulation of spike timing in visual cortical circuits

A train of action potentials (a spike train) can carry information in both the average firing rate and the pattern of spikes in the train. But can such a spike-pattern code be supported by cortical circuits? Neurons in vitro produce a spike pattern in response to the injection of a fluctuating current. However, cortical neurons in vivo are modulated by local oscillatory neuronal activity and by top-down inputs. In a cortical circuit, precise spike patterns thus reflect the interaction between internally generated activity and sensory information encoded by input spike trains. We review the evidence for precise and reliable spike timing in the cortex and discuss its computational role.     

Spike timing and synaptic plasticity in the premotor pathway of birdsong

The neural circuits of birdsong appear to utilize specific time delays in their operation. In particular, the anterior forebrain pathway (AFP) is implicated in an approximately 40- to 50- ms time delay, T, playing a role in the relative timing of premotor signals from the nucleus HVc to the nucleus robust nucleus of the archistratium (RA) and control/learning signals from the nucleus lateral magnocellular nucleus of the anterior neostratium (lMAN) to RA. Using a biophysical model of synaptic plasticity based on experiments on mammalian hippocampal and neocortical pyramidal neurons, we propose an understanding of this 40- to 50- ms delay. The biophysical model describes the influence of Ca²⁺ influx into the postsynaptic RA cells through NMDA and AMPA receptors and the induction of LTP and LTD through complex metabolic pathways. The delay, T, between HVc RA premotor signals and lMAN RA control/learning signals plays an essential role in determining if synaptic plasticity is induced by signaling from each pathway into RA. If T is substantially larger than 40 ms, no plasticity is induced. If T is much less than 40 ms, only potentiation is expected. If T 40 ms, the sign of synaptic plasticity is sensitive to T. Our results suggest that changes in T may influence learning and maintenance of birdsong. We investigate the robustness of this result to noise and to the removal of the Ca²⁺ contribution from lMAN RA NMDA receptors.     

Systems-level modeling of neuronal circuits for leech swimming

This paper describes a mathematical model of the neuronal central pattern generator (CPG) that controls the rhythmic body motion of the swimming leech. The systems approach is employed to capture the neuronal dynamics essential for generating coordinated oscillations of cell membrane potentials by a simple CPG architecture with a minimal number of parameters. Based on input/output data from physiological experiments, dynamical components (neurons and synaptic interactions) are first modeled individually and then integrated into a chain of nonlinear oscillators to form a CPG. We show through numerical simulations that the values of a few parameters can be estimated within physiologically reasonable ranges to achieve good fit of the data with respect to the phase, amplitude, and period. This parameter estimation leads to predictions regarding the synaptic coupling strength and intrinsic period gradient along the nerve cord, the latter of which agrees qualitatively with experimental observations.     

Innate synchronous oscillations in freely-organized small neuronal circuits

Background

Information processing in neuronal networks relies on the network''s ability to generate temporal patterns of action potentials. Although the nature of neuronal network activity has been intensively investigated in the past several decades at the individual neuron level, the underlying principles of the collective network activity, such as the synchronization and coordination between neurons, are largely unknown. Here we focus on isolated neuronal clusters in culture and address the following simple, yet fundamental questions: What is the minimal number of cells needed to exhibit collective dynamics? What are the internal temporal characteristics of such dynamics and how do the temporal features of network activity alternate upon crossover from minimal networks to large networks?

Methodology/Principal Findings

We used network engineering techniques to induce self-organization of cultured networks into neuronal clusters of different sizes. We found that small clusters made of as few as 40 cells already exhibit spontaneous collective events characterized by innate synchronous network oscillations in the range of 25 to 100 Hz. The oscillation frequency of each network appeared to be independent of cluster size. The duration and rate of the network events scale with cluster size but converge to that of large uniform networks. Finally, the investigation of two coupled clusters revealed clear activity propagation with master/slave asymmetry.

Conclusions/Significance

The nature of the activity patterns observed in small networks, namely the consistent emergence of similar activity across networks of different size and morphology, suggests that neuronal clusters self-regulate their activity to sustain network bursts with internal oscillatory features. We therefore suggest that clusters of as few as tens of cells can serve as a minimal but sufficient functional network, capable of sustaining oscillatory activity. Interestingly, the frequencies of these oscillations are similar those observed in vivo.     

Adult neurogenesis and functional plasticity in neuronal circuits

The adult brain is a plastic place. To ensure that the mature nervous system's control of behaviour is flexible in the face of a varying environment, morphological and physiological changes are possible at many levels, including that of the entire cell. In two areas of the adult brain - the olfactory bulb and the dentate gyrus - new neurons are generated throughout life and form an integral part of the normal functional circuitry. This process is not fixed, but highly modulated, revealing a plastic mechanism by which the brain's performance can be optimized for a given environment. The functional benefits of this whole-cell plasticity, however, remain a matter for debate.     

Cholecystokinin: a multi-functional molecular switch of neuronal circuits

Cholecystokinin (CCK), a peptide originally discovered in the gastrointestinal tract, is one of the most abundant and widely distributed neuropeptides in the brain. In spite of its abundance, recent data indicate that CCK modulates intrinsic neuronal excitability and synaptic transmission in a surprisingly cell-type specific manner, acting as a key molecular switch to regulate the functional output of neuronal circuits. The central importance of CCK in neuronal networks is also reflected in its involvement in a variety of neuropsychiatric and neurological disorders including panic attacks and epilepsy.     

The evolution of neuronal circuits underlying species-specific behavior.

The nervous system is evolutionarily conservative compared to the peripheral appendages that it controls. However, species-specific behaviors may have arisen from very small changes in neuronal circuits. In particular, changes in neuromodulatory systems may allow multifunctional circuits to produce different sets of behaviors in closely related species. Recently, it was demonstrated that even species differences in complex social behavior may be attributed to a change in the promoter region of a single gene regulating a neuromodulatory action.     

Circadian remodeling of neuronal circuits involved in rhythmic behavior

Clock output pathways are central to convey timing information from the circadian clock to a diversity of physiological systems, ranging from cell-autonomous processes to behavior. While the molecular mechanisms that generate and sustain rhythmicity at the cellular level are well understood, it is unclear how this information is further structured to control specific behavioral outputs. Rhythmic release of pigment dispersing factor (PDF) has been proposed to propagate the time of day information from core pacemaker cells to downstream targets underlying rhythmic locomotor activity. Indeed, such circadian changes in PDF intensity represent the only known mechanism through which the PDF circuit could communicate with its output. Here we describe a novel circadian phenomenon involving extensive remodeling in the axonal terminals of the PDF circuit, which display higher complexity during the day and significantly lower complexity at nighttime, both under daily cycles and constant conditions. In support to its circadian nature, cycling is lost in bona fide clockless mutants. We propose this clock-controlled structural plasticity as a candidate mechanism contributing to the transmission of the information downstream of pacemaker cells.