Evangelos G. Antzoulatos

Learning insights transmitted by glutamate

Plasticity of the Aplysia sensorimotor synapse plays a crucial role in learning and memory of withdrawal reflexes. During the past ten years, a growing body of evidence has indicated that the sensorimotor synapse is glutamatergic. This new information has guided several studies that implicate AMPA and NMDA receptors in synaptic plasticity. However, further work is necessary to delineate the exact properties of the postsynaptic receptors, and their role in transmission and plasticity. Despite the still incomplete picture of the intrinsic properties of the sensorimotor synapse, identifying the endogenous transmitter has provided a foundation for new avenues of research, the results of which will further improve our understanding of the neurobiology of learning and memory.

Burst-Induced Synaptic Depression and Its Modulation Contribute to Information Transfer at Aplysia Sensorimotor Synapses: Empirical and Computational Analyses

The Aplysia sensorimotor synapse is a key site of plasticity for several simple forms of learning. Plasticity of this synapse has been extensively studied, albeit primarily with individual action potentials elicited at low frequencies. Yet, the mechanosensory neurons fire high-frequency bursts in response to even moderate tactile stimuli delivered to the skin. In the present study, we extend this analysis to show that sensory neurons also fire bursts in the range of 1-60 Hz in response to electrical stimuli similar to those used in behavioral studies of sensitization. Intracellular stimulation of sensory neurons to fire a burst of action potentials at 10 Hz for 1 sec led to significant homosynaptic depression of postsynaptic responses. The depression was transient and fully recovered within 10 min. During the burst, the steady-state depressed phase of the postsynaptic response, which was only 20% of the initial EPSP of the burst, still contributed to firing the motor neuron. To explore the functional contribution of transient homosynaptic depression to the response of the motor neuron, computer simulations of the sensorimotor synapse with and without depression were compared. Depression allowed the motor neuron to produce graded responses over a wide range of presynaptic input strength. In addition, enhancement of synaptic transmission throughout a burst increased motor neuron output substantially more than did preferential enhancement of the initial phase of a burst. Thus, synaptic depression increased the dynamic range of the sensorimotor synapse and can, in principle, have a profound effect on information processing.

Long-Term Sensitization Training Produces Spike Narrowing in Aplysia Sensory Neurons

Both short- and long-term sensitization of withdrawal reflexes of Aplysia are attributable at least in part to facilitation of the sensorimotor synapse. Previously, short-term synaptic facilitation has been associated with spike broadening and no change in temporal dynamics of burst transmission. In the present study, we examined whether long-term sensitization (LTS) is also associated with spike broadening and whether long-term synaptic facilitation is accompanied by changes in temporal dynamics. The results indicate that the temporal dynamics of the sensorimotor synapse are preserved after long-term facilitation. However, in contrast to short-term sensitization, LTS was accompanied by spike narrowing. The spike narrowing was observed both in centrally triggered spikes in isolated ganglia and in peripherally triggered spikes in reduced tail preparations. In addition, in reduced tail preparations, fewer spike failures in the afferent discharge of sensory neurons occurred in response to tail stimulation after ipsilateral LTS. Collectively, the results reveal that long-term sensitization affects the spike waveform of sensory neurons and enhances the sensory neuron responses to peripheral stimuli, but does not modify the synaptic dynamics of homosynaptic depression.

Synchronous beta rhythms of frontoparietal networks support only behaviorally relevant representations

Categorization has been associated with distributed networks of the primate brain, including the prefrontal cortex (PFC) and posterior parietal cortex (PPC). Although category-selective spiking in PFC and PPC has been established, the frequency-dependent dynamic interactions of frontoparietal networks are largely unexplored. We trained monkeys to perform a delayed-match-to-spatial-category task while recording spikes and local field potentials from the PFC and PPC with multiple electrodes. We found category-selective beta- and delta-band synchrony between and within the areas. However, in addition to the categories, delta synchrony and spiking activity also reflected irrelevant stimulus dimensions. By contrast, beta synchrony only conveyed information about the task-relevant categories. Further, category-selective PFC neurons were synchronized with PPC beta oscillations, while neurons that carried irrelevant information were not. These results suggest that long-range beta-band synchrony could act as a filter that only supports neural representations of the variables relevant to the task at hand. DOI: http://dx.doi.org/10.7554/eLife.17822.001

4.03 – Sensitization and Habituation: Invertebrate

Invertebrates have been used extensively as simple model systems for the study of the mechanisms underlying learning and memory at the network, cellular, and molecular levels. In Aplysia and several other invertebrates, the two most characteristic forms of nonassociative learning, habituation and sensitization, rely on modifications of early afferent neurons and their synapses onto target cells. Whereas habituation is primarily attributed to activity-dependent synaptic depression, sensitization is often attributed to the facilitatory actions of neuromodulators, such as serotonin. This chapter reviews some of this progress with a particular emphasis on mechanisms of habituation and sensitization in the marine mollusc Aplysia.

Learning and Memory in Invertebrates: Aplysia

The marine invertebrate Aplysia has been used extensively as a model system to study learning and memory, allowing the dissection of learning mechanisms at the network, cellular, and molecular levels. The withdrawal reflexes of Aplysia display associative and nonassociative learning, which rely on modifications of sensory neurons and their synapses onto target cells. Whereas habituation is attributed to activity-dependent synaptic depression, sensitization, and classical conditioning have been attributed to the facilitatory actions of serotonin. Finally, the feeding behavior of Aplysia has recently emerged as a useful model system for the mechanistic comparison of classical and operant conditioning.