Impact of cognitive stimulation on ripples within human epileptic and non-epileptic hippocampus

Background: Until now there has been no way of distinguishing between physiological and epileptic hippocampal ripples in intracranial recordings. In the present study we addressed this by investigating the effect of cognitive stimulation on interictal high frequency oscillations in the ripple range (80-250 Hz) within epileptic (EH) and non-epileptic hippocampus (NH). Methods: We analyzed depth EEG recordings in 10 patients with intractable epilepsy, in whom hippocampal activity was recorded initially during quiet wakefulness and subsequently during a simple cognitive task. Using automated detection of ripples based on amplitude of the power envelope, we analyzed ripple rate (RR) in the cognitive and resting period, within EH and NH. Results: Compared to quiet wakefulness we observed a significant reduction of RR during cognitive stimulation in EH, while it remained statistically marginal in NH. Further, we investigated the direct impact of cognitive stimuli on ripples (i.e. immediately post-stimulus), which showed a transient statistically significant suppression of ripples in the first second after stimuli onset in NH only. Conclusion: Our results point to a differential reactivity of ripples within EH and NH to cognitive stimulation

Neural Computation via Neural Geometry: A Place Code for Inter-whisker Timing in the Barrel Cortex?

The place theory proposed by Jeffress (1948) is still the dominant model of how the brain represents the movement of sensory stimuli between sensory receptors. According to the place theory, delays in signalling between neurons, dependent on the distances between them, compensate for time differences in the stimulation of sensory receptors. Hence the location of neurons, activated by the coincident arrival of multiple signals, reports the stimulus movement velocity. Despite its generality, most evidence for the place theory has been provided by studies of the auditory system of auditory specialists like the barn owl, but in the study of mammalian auditory systems the evidence is inconclusive. We ask to what extent the somatosensory systems of tactile specialists like rats and mice use distance dependent delays between neurons to compute the motion of tactile stimuli between the facial whiskers (or ‘vibrissae’). We present a model in which synaptic inputs evoked by whisker deflections arrive at neurons in layer 2/3 (L2/3) somatosensory ‘barrel’ cortex at different times. The timing of synaptic inputs to each neuron depends on its location relative to sources of input in layer 4 (L4) that represent stimulation of each whisker. Constrained by the geometry and timing of projections from L4 to L2/3, the model can account for a range of experimentally measured responses to two-whisker stimuli. Consistent with that data, responses of model neurons located between the barrels to paired stimulation of two whiskers are greater than the sum of the responses to either whisker input alone. The model predicts that for neurons located closer to either barrel these supralinear responses are tuned for longer inter-whisker stimulation intervals, yielding a topographic map for the inter-whisker deflection interval across the surface of L2/3. This map constitutes a neural place code for the relative timing of sensory stimuli

Finding the engram.

Many attempts have been made to localize the physical trace of a memory, or engram, in the brain. However, until recently, engrams have remained largely elusive. In this Review, we develop four defining criteria that enable us to critically assess the recent progress that has been made towards finding the engram. Recent \u27capture\u27 studies use novel approaches to tag populations of neurons that are active during memory encoding, thereby allowing these engram-associated neurons to be manipulated at later times. We propose that findings from these capture studies represent considerable progress in allowing us to observe, erase and express the engram

Metabotropic action of postsynaptic kainate receptors triggers hippocampal long-term potentiation

Long-term potentiation (LTP) in the rat hippocampus is the most extensively studied cellular model for learning and memory. Induction of classical LTP involves an NMDA receptor- and calcium-dependent increase in functional synaptic AMPA receptors mediated by enhanced recycling of internalized AMPA receptors back to the postsynaptic membrane. Here we report a novel, physiologically relevant NMDA receptor-independent mechanism that drives increased AMPA receptor recycling and LTP. This pathway requires the metabotropic action of kainate receptors and activation of G-protein, protein kinase C and phospholipase C. Like classical LTP, kainate receptor-dependent LTP recruits recycling endosomes to spines, enhances synaptic recycling of AMPA receptors to increase their surface expression and elicits structural changes in spines, including increased growth and maturation. These data reveal a new and previously unsuspected role for postsynaptic kainate receptors in the induction of functional and structural plasticity in the hippocampus