Theta synchronization in the limbic system: the role of Gudden's tegmental nuclei.

Theta rhythm is most prominent in the hippocampus but has also been recorded in other cortical and limbic structures and can play an important role in functional coupling of widely separated structures responsible for different components of the memory building process. Here we demonstrate in the rat that neuronal activity exhibiting strong state-dependent synchrony with rhythmic hippocampal electroencephalogram is present also at the brainstem level, specifically in the relatively small tegmental nuclei of Gudden intimately connected with the limbic forebrain. We found that during theta states, either occurring spontaneously or triggered by sensory stimulation in the urethane anaesthetized rat, all neurons in the anterior and ventral tegmental nuclei exhibited a consistent switch from irregular discharges to rhythmic bursts. The switch between these patterns closely matched the analogous transformations in the hippocampal EEG, but the level of synchrony between the two signals varied depending on the level of theta activation. During sensory stimulation, when theta is faster and more regular, the rhythmic bursts in the tegmentum showed extremely high coherence (up to 0.96) with hippocampal field potentials. During spontaneous theta, the average coherence was lower but still highly significant (0.62). Gudden's nuclei are reciprocally connected to the mammillary body complex (MB) occupying a strategic position at the gateway of hippocampofugal connections organized in the Papez circuit. Thus, coupling between the MB-Gudden circuit and the hippocampus and consequently the neuronal traffic through the Papez circuit and hence the assembly of limbic structures connected to the hippocampus may vary according to the activity in these specific brainstem nuclei.

Stimulation of the mesencephalic locomotor region elicits controlled swimming in semi-intact lampreys.

The role of the mesencephalic locomotor region (MLR) in initiating and controlling the power of swimming was studied in semi-intact preparations of larval and adult sea lampreys. The brain and the rostral portion of the spinal cord were exposed in vitro, while the intact caudal two-thirds of the body swam freely in the Ringer's-containing chamber. Electrical microstimulation (2-10 Hz; 0. 1-5.0 microA) within a small periventricular region in the caudal mesencephalon elicited well-coordinated and controlled swimming that began within a few seconds after the onset of stimulation and lasted throughout the stimulation period. Swimming stopped several seconds after the end of stimulation. The power of swimming, expressed by the strength of the muscle contractions and the frequency and the amplitude of the lateral displacement of the body or tail, increased as the intensity or frequency of the stimulating current were increased. Micro-injection of AMPA, an excitatory amino acid agonist, into the MLR also elicited active swimming. Electrical stimulation of the MLR elicited large EPSPs in reticulospinal neurons (RS) of the middle rhombencephalic reticular nucleus (MRRN), which also displayed rhythmic activity during swimming. The retrograde tracer cobalt-lysine was injected into the MRRN and neurons (dia. 10-20 microm) were labelled in the MLR, indicating that this region projects to the rhombencephalic reticular formation. Taken together, the present results indicate that, as higher vertebrates, lampreys possess a specific mesencephalic region that controls locomotion, and the effects onto the spinal cord are relayed by brainstem RS neurons.

A cellular mechanism for the transformation of a sensory input into a motor command.

The initiation and control of locomotion largely depend on processing of sensory inputs. The cellular bases of locomotion have been extensively studied in lampreys where reticulospinal (RS) neurons constitute the main descending system activating and controlling the spinal locomotor networks. Ca(2+) imaging and intracellular recordings were used to study the pattern of activation of RS neurons in response to cutaneous stimulation. Pressure applied to the skin evoked a linear input/output relationship in RS neurons until a threshold level, at which a depolarizing plateau was induced, the occurrence of which was associated with the onset of swimming activity in a semi-intact preparation. The occurrence of a depolarizing plateau was abolished by blocking the NMDA receptors that are located on RS cells. Moreover, the depolarizing plateaus were accompanied by a rise in [Ca(2+)](i), and an intracellular injection of the Ca(2+) chelator BAPTA into single RS cells abolished the plateaus, suggesting that the latter are Ca(2+) dependent and rely on intrinsic properties of RS cells. The plateaus were shown to result from the activation of a Ca(2+)-activated nonselective cation current that maintains the cell in a depolarized state. It is concluded that this intrinsic property of the RS neuron is then responsible for the transformation of an incoming sensory signal into a motor command that is then forwarded to the spinal locomotor networks.

Role of sensory-evoked NMDA plateau potentials in the initiation of locomotion.

Reticulospinal (RS) neurons constitute the main descending motor system of lampreys. This study reports on natural conditions whereby N-methyl-D-aspartate (NMDA)-mediated plateau potentials were elicited and associated with the onset of locomotion. Reticulospinal neurons responded in a linear fashion to mild skin stimulation. With stronger stimuli, large depolarizing plateaus with spiking activity were elicited and were accompanied by swimming movements. Calcium imaging revealed sustained intracellular calcium rise upon sensory stimulation. Blocking NMDA receptors on RS neurons prevented the plateau potentials as well as the associated rise in intracellular calcium. Thus, the activation of NMDA receptors mediates a switch from sensory-reception mode to a motor command mode in RS neurons.

5-HT innervation of reticulospinal neurons and other brainstem structures in lamprey.

In order to determine if reticulospinal neurons involved in the control of locomotion and responsive to exogenously applied 5-hydroxytryptamine (5-HT) are innervated by fibers that contain serotonin, the serotoninergic innervation of reticulospinal neurons, identified by retrograde labeling with fluorescein-conjugated dextran-amine (FDA), was investigated by immunohistochemistry in the lamprey brainstem. A widespread distribution of 5-HT immunoreactive (5-HT-ir) fibers was seen within the basal plate of the brainstem, an area containing reticulospinal somata and dendritic aborizations. Numerous 5-HT varicose fibers were found in close relation to large reticulospinal cell bodies, particularly in the middle and anterior rhombencephalic reticular nuclei (MRRN and ARRN). Some of these reticulospinal somata were surrounded by a very dense pericellular 5-HT innervation. 5-HT-ir fibers were also seen in other brain structures that are known to influence reticulospinal neurons such as the rhombencephalic alar plate containing sensory relay interneurons, cranial nerves (III-X), cerebellum, and tectum. These findings suggest that, as in the spinal cord, motor behavior controlled by reticulospinal neurons may be subject to a serotoninergic modulation.

5-Hydroxytryptamine modulates spike frequency regulation in reticulospinal neurons involved in the control of locomotion in lamprey.

To investigate the effects of 5-hydroxytryptamine (5-HT) on reticulospinal neurons involved in the initiation and control of locomotion in lamprey, 5-HT (10 mM) was locally pressure ejected on the dorsal surface of the brainstem during intracellular recordings from identified reticulospinal neurons in the in vitro brainstem-spinal cord preparation. 5-HT induced a reduction of the late afterhyperpolarization (AHP) following the spike due to a reduction of a Ca(2+)-activated K+ current. In addition, 5-HT caused a resting membrane hyperpolarization in a proportion of these cells. Due to the 5-HT induced reduction of the AHP, reticulospinal cells, including those that became hyperpolarized by an application of 5-HT, discharged at a higher rate after 5-HT as a response to the same excitatory drive.

Synaptic effects of intraspinal stretch receptor neurons mediating movement-related feedback during locomotion.

The flattened lamprey spinal cord contains stretch-sensitive edge cells located along the lateral margin, with dendritic processes sensing the lateral bending of the cord during each swim cycle. These intraspinal stretch receptor neurons provide movement-related sensory feedback input to the generator network for locomotion causing a powerful entrainment of the rhythm. In order to elucidate the synaptic effects of edge cells we have performed paired intracellular recordings and staining with Lucifer yellow. Monosynaptic connections that may explain entrainment were found to locomotor central pattern generator interneurons. Edge cells with an ipsilateral axon elicited excitatory postsynaptic potentials (EPSPs) in ipsilateral interneurons. In addition, such edge cells evoked kainate/quisqualate receptor mediated EPSPs in ipsilateral motoneurons. This pathway mediates an intraspinal stretch reflex analogous to the muscle spindle mediated stretch reflex of mammals. Edge cells with a contralateral axon produced monosynaptic glycinergic IPSPs in contralateral neurons, including contralateral edge cells.

Odor-related bulbar EEG spatial pattern analysis during appetitive conditioning in rabbits.

Mildly thirsty rabbits were classically conditioned by reinforcement with water to give a discriminative licking response to the presentation of odors. The jaw movement component of the licking conditioned response (JM CR) was elicited only by the reinforced odor; an increase in the relative frequency of sniffing (RR CR) occurred to both reinforced (CS+) and nonreinforced (CS-) odors. Oscillatory electroencephalographic bursts of high-frequency (40-80 Hz) potentials were recorded epidurally from the lateral olfactory bulb with 64-electrode arrays (8 X 8, 3.5 X 3.5 mm) chronically implanted. Emphasis was on comparing bursts during odor presentation with bursts preceding odor arrival on each trial. A "detection" burst was characterized as occurring immediately after odor arrival and before the sniff response. "Discrimination" bursts occurred during the RR CR and before the JM CR onset. Significant air-odor burst differences (together with sniffing) occurred through up to six sessions for both CS+ and CS- odors for "discrimination" bursts but not for "detection" bursts.

Synaptic competition in developmental binocular plasticity.

A mathematical model of the possible physiological and biochemical mechanisms responsible for the changes occurring during binocular development is proposed. The model is based on the mechanisms postulated for the occurrence of well known plastic processes, such as post-tetanic potentiation, sensitization and heterosynaptic inhibition. Because all these processes are of presynaptic nature, we have postulated that the plastic processes occurring during development are of the same nature. The factors we have considered in our model are: the transmitter pool size, the mobilization or synthesis of the transmitter, the transmitter release by the physiological stimulus, the neuroendocrine and genetic activity. With this model we have simulated the following phenomena during ocular development: (1) normal binocular development; (2) monocular deprivation, including the effects of reversing the occluded eye; (3) binocular deprivation and recovery; and (4) effects of alternating deprivation on mature binocularity. The model also allows us to explain in a natural way the possible changes occurring during denervation or disuse.