Fictive rhythmic motor patterns induced by NMDA in an in vitro brain stem-spinal cord preparation from an adult urodele.
(41/6550)
An in vitro brain stem-spinal cord preparation from an adult urodele (Pleurodeles waltl) was developed in which two fictive rhythmic motor patterns were evoked by bath application of N-methyl-D-aspartate (NMDA; 2.5-10 microM) with D-serine (10 microM). Both motor patterns displayed left-right alternation. The first pattern was characterized by cycle periods ranging between 2.4 and 9. 0 s (4.9 +/- 1.2 s, mean +/- SD) and a rostrocaudal propagation of the activity in consecutive ventral roots. The second pattern displayed longer cycle periods (8.1-28.3 s; 14.2 +/- 3.6 s) with a caudorostral propagation. The two patterns were inducible after a spinal transection at the first segment. Preliminary experiments on small pieces of spinal cord further suggested that the ability for rhythm generation is distributed along the spinal cord of this preparation. This study shows that the in vitro brain stem-spinal cord preparation from Pleurodeles waltl may be a useful model to study the mechanisms underlying the different axial motor patterns and the flexibility of the neural networks involved. (+info)
Integrative properties of the Pe1 neuron, a unique mushroom body output neuron.
(42/6550)
A mushroom body extrinsic neuron, the Pe1 neuron, connects the peduncle of the mushroom body (MB) with two areas of the protocerebrum in the honeybee brain, the lateral protocerebral lobe (LPL) and the ring neuropil around the alpha-lobe. Each side of the bee brain contains only one Pe1 neuron. Using a combination of intracellular recording and neuroanatomical techniques we analyzed its properties of integrative processing of the different sensory modalities. The Pe1 neuron responds to visual, mechanosensory, and olfactory stimuli. The responses are broadly tuned, consisting of a sustained increase of spike frequency to the onset and offset of light flashes, to horizontal and vertical movements of extended objects, to mechanical stimuli applied to the antennae or mouth parts, and to all olfactory stimuli tested (29 chemicals). These multisensory properties are reflected in its dendritic organization. Serial reconstructions of intracellularly stained Pe1 neurons using confocal microscopy reveal that the Pe1 neuron arborizes throughout all layers of MB peduncle with finger-like, vertically oriented dendrites. The peduncle of the MB is formed by the axons of Kenyon cells, whose dendritic inputs are organized in modality-specific subcompartments of the calyx region. The peduncular arborization indicates that the Pe1 neuron receives input from Kenyon cells of all calycal subcompartments. Because the Pe1 neuron changes its odor responses transiently as a consequence of olfactory learning, we hypothesize that the multimodal response properties might have a role in memory consolidation and help to establish contextual references in the long-term trace. (+info)
Cerebellar guidance of premotor network development and sensorimotor learning.
(43/6550)
Single unit and imaging studies have shown that the cerebellum is especially active during the acquisition phase of certain motor and cognitive tasks. These data are consistent with the hypothesis that particular sensorimotor procedures are acquired and stored in the cerebellar cortex and that this knowledge can then be exported to the cerebral cortex and premotor networks for more efficient execution. In this article we present a model to illustrate how the cerebellar cortex might guide the development of cortical-cerebellar network connections and how a similar mechanism operating in the adult could mediate the exportation of sensorimotor knowledge from the cerebellum to the motor cortex. The model consists of a three-layered recurrent network representing the cerebello-thalamocortical-ponto-cerebellar limb premotor network. The cerebellar cortex is not explicitly modeled. Our simulations show that Hebbian learning combined with weight normalization allows the emergence of reciprocal and modular structure in the limb premotor network. Reciprocal connections allow activity to reverberate around specific loops. Modularity organizes the connections into specific channels. Furthermore, we show that cerebellar learning can be exported to motor cortex through these modular and reciprocal premotor circuits. In particular, we simulate developmental alignment of visuomotor relations and their realignment as a consequence of prism exposure. The exportation of sensorimotor knowledge from the cerebellum to the motor cortex may allow faster and more efficient execution of learned motor responses. (+info)
Effect of varying the intensity and train frequency of forelimb and cerebellar mossy fiber conditioned stimuli on the latency of conditioned eye-blink responses in decerebrate ferrets.
(44/6550)
To study the role of the mossy fiber afferents to the cerebellum in classical eye-blink conditioning, in particular the timing of the conditioned responses, we compared the effects of varying a peripheral conditioned stimulus with the effects of corresponding variations of direct stimulation of the mossy fibers. In one set of experiments, decerebrate ferrets were trained in a Pavlovian eye-blink conditioning paradigm with electrical forelimb train stimulation as conditioned stimulus and electrical periorbital stimulation as the unconditioned stimulus. When stable conditioning had been achieved, the effect of increasing the intensity or frequency of the forelimb stimulation was tested. By increasing the intensity from 1 to 2 mA, or the train frequency from 50 to 100 Hz, an immediate decrease was induced in both the onset latency and the latency to peak of the conditioned response. If the conditioned stimulus intensity/frequency was maintained at the higher level, the response latencies gradually returned to preshift values. In a second set of experiments, the forelimb stimulation was replaced by direct train stimulation of the middle cerebellar peduncle as conditioned stimulus. Varying the frequency of the stimulus train between 50 and 100 Hz had effects that were almost identical to those obtained when using a forelimb conditioned stimulus. The functional meaning of the latency effect is discussed. It is also suggested that the results support the view that the conditioned stimulus is transmitted through the mossy fibers and that the mechanism for timing the conditioned response is situated in the cerebellum. (+info)
Conditioned response timing and integration in the cerebellum.
(45/6550)
Classical conditioning procedures instill knowledge about the temporal relationships between events. The unconditioned stimulus (US) is the event to be timed. The conditioned response (CR) is viewed as a prediction of the imminence of the US. Knowledge of the elapsed time between conditioned stimuli (CSs) and US delivery is expressed in the topological features of the CR. The peak amplitude of the CR coincides with the timing of the US. A simple connectionist network based on Sutton and Barto's Time Derivative (TD) Model of Pavlovian Reinforcement provides a mechanism that can account for and simulate CR timing in a variety of protocols. This article describes extensions of the model to predictive timing under temporal uncertainty. The model is expressed in terms of equations that operate in real time according to a competitive learning rule. The unfolding of time from the onsets and offsets of events such as CSs is represented by the propagation of activity along a sequence of time-tagged elements. The model can be aligned with anatomical circuits of the cerebellum and brain stem that are essential for learning and performance of conditioned eye-blink responses. (+info)
Theta/gamma networks with slow NMDA channels learn sequences and encode episodic memory: role of NMDA channels in recall.
(46/6550)
This paper examines the role of slow N-methyl-D-aspartate (NMDA) channels (deactivation approximately 150 msec) in networks that multiplex different memories in different gamma subcycles of a low frequency theta oscillation. The NMDA channels are in the synapses of recurrent collaterals and govern synaptic modification in accord with known physiological properties. Because slow NMDA channels have a time constant that spans several gamma cycles, synaptic connections will form between cells that represent different memories. This enables brain structures that have slow NMDA channels to store heteroassociative sequence information in long-term memory. Recall of this stored sequence information can be initiated by presentation of initial elements of the sequence. The remaining sequence is then recalled at a rate of one memory every gamma cycle. A new role for the NMDA channel suggested by our finding is that recall at gamma frequency works well if slow NMDA channels provide the dominant component of the EPSP at the synapse of recurrent collaterals: The slow onset of these channels and their long duration allows the firing of one memory during one gamma cycle to trigger the next memory during the subsequent gamma cycle. An interesting feature of the readout mechanism is that the activation of a given memory is due to cumulative input from multiple previous memories in the stored sequence, not just the previous one. The network thus stores sequence information in a doubly redundant way: Activation of a memory depends on the strength of synaptic inputs from multiple cells of multiple previous memories. The cumulative property of sequence storage has support from the psychophysical literature. Cumulative learning also provides a solution to the disambiguation problem that occurs when different sequences have a region of overlap. In a final set of simulations, we show how coupling an autoassociative network to a heteroassociative network allows the storage of episodic memories (a unique sequence of briefly occurring known items). The autoassociative network (cortex) captures the sequence in short-term memory and provides the accurate, time-compressed repetition required to drive synaptic modification in the heteroassociative network (hippocampus). This is the first mechanistically detailed model showing how known brain properties, including network oscillations, recurrent collaterals, AMPA channels, NMDA channel subtypes, the ADP, and the AHP can act together to accomplish memory storage and recall. (+info)
Activation of intrinsic hippocampal theta oscillations by acetylcholine in rat septo-hippocampal cocultures.
(47/6550)
1. Oscillatory electro-encephalographic activity at theta frequencies (4-15 Hz) can be recorded from the hippocampus in vivo and depends on intact septal projections. The hypothesis that these oscillations are imposed on the hippocampus by rhythmically active septal inputs was tested using dual intracellular recordings from CA1 and CA3 pyramidal cells in septo-hippocampal cocultures. 2. Septo-hippocampal cocultures displayed spontaneous oscillatory synaptic activity at theta frequencies. In CA3 cells, EPSP/IPSP sequences predominated, whereas only EPSPs were apparent in CA1 cells. Synaptic potentials in CA3 cells preceded those in CA1 cells by 5-10 ms. 3. Oscillatory synaptic activity was blocked in cocultures by the muscarinic antagonist atropine (0.1 microM), facilitated but unchanged in frequency upon application of the acetylcholinesterase inhibitor neostigmine (1 microM), and not seen in hippocampal monocultures. 4. The muscarinic agonist methacholine (5-20 nM) induced oscillatory synaptic activity at 4-15 Hz in hippocampal monocultures, which was identical to that occurring spontaneously in septo-hippocampal cocultures. 5. Synaptic theta activity was observed in cocultures of septal tissue with subdissected hippocampal slices containing area CA3 alone, but not in septo-CA1 cocultures. 6. We conclude that oscillatory synaptic activity at theta frequencies, with similar characteristics to theta activity in vivo, can be generated by the hippocampal network in response to activation of muscarinic receptors by synaptically released acetylcholine from septal afferents. Furthermore, the oscillatory activity is determined by mechanisms intrinsic to the hippocampal circuitry, particularly area CA3. Rhythmic septal input is not required. (+info)
Modulation of the hyperpolarization-activated cation current of rat thalamic relay neurones by intracellular pH.
(48/6550)
1. Properties of the hyperpolarization-activated cation current (Ih) were investigated in thalamocortical neurones of an in vitro slice preparation of the rat ventrobasal thalamic complex (VB) before and during changes of pipette pH (pHp), intracellular pH (pHi) and bath pH (pHb) using the whole-cell patch-clamp technique and fluorescence ratio imaging of the pH indicator 2',7'-bis(carboxyethyl)-5(and -6)-carboxyfluorescein (BCECF). 2. Recording of Ih with predefined pHp revealed significant shifts in the voltage dependence of Ih activation (V ) of 4-5 mV to more positive values for a pHp of 7.5 and 2-3 mV to more negative values for a pHp of 6.7 as compared to control values (pHp = 7.1). 3. Application of the weak acid lactate (20 mM), which produced a slow monophasic intracellular acidification, induced a reversible negative shift of V of up to 3 mV. Application of 20 mM TMA, which caused a distinct intracellular alkalinization, shifted V to 4-5 mV more positive values. 4. In slices bathed in Hepes-buffered saline, no significant pHo dependence of Ih was observed. Changing pHo by altering the extracellular [HCO3-] in the presence of constant pCO2 also revealed no significant pHo dependence of Ih. 5. Rhythmic stimulation of thalamocortical neurones with repetitive depolarizing pulse trains caused an intracellular acidification, which reversibly decreased the amplitude and time course of activation of Ih. 6. The results of the present study indicate that shifts in pHi result in a significant modulation of the gating properties of Ih channels in TC neurones. Through this mechanism activity-dependent shifts in pHi may contribute to the up- and downregulation of Ih. (+info)