Tooth loss, apolipoprotein E, and decline in delayed word recall.

Our previous research suggests an association between a low number of teeth and increased risk of dementia. The aim of the present study was to determine if a low number of teeth is specifically related to memory decline as evidenced by low Delayed Word Recall scores. In addition, we examined the combined effect of a low number of teeth and the apolipoprotein E epsilon4 allele on Delayed Word Recall scores. We hypothesized that the scores of those who had the allele and a low number of teeth (0-9) would decline more rapidly over time than those participants with a greater number of teeth who lacked the allele. We found that individuals with both risk factors (the allele and fewer teeth) had lower Delayed Word Recall scores at the first examination and declined more quickly compared with participants with neither of these risk factors or with either risk factor alone.

Neuronal control of turtle hindlimb motor rhythms.

The turtle, Trachemys scripta elegans, uses its hindlimb during the rhythmic motor behaviors of walking, swimming, and scratching. For some tasks, one or more motor strategies or forms may be produced, e.g., forward swimming or backpaddling. This review discusses experiments that reveal characteristics of the spinal neuronal networks producing these motor behaviors. Limb-movement studies show shared properties such as rhythmic alternation between hip flexion and hip extension, as well as variable properties such as the timing of knee extension in the cycle of hip movements. Motor-pattern studies show shared properties such as rhythmic alternation between hip flexor and hip extensor motor activities, as well as variable properties such as modifiable timing of knee extensor motor activity in the cycle of hip motor activity. Motor patterns also display variations such as the hip-extensor deletion of rostral scratching. Neuronal-network studies reveal mechanisms responsible for movement and motor-pattern properties. Some interneurons in the spinal cord have shared activities, e.g., each unit is active during more than one behavior, and have distinct characteristics, e.g., each unit is most excited during a specific behavior. Interneuronal recordings during variations support the concept of modular organization of central pattern generators in the spinal cord.

Step, swim, and scratch motor patterns in the turtle.

The turtle generates a variety of coordinated hindlimb movements, including different forms of locomotion and scratching. The intact turtle produces forward step, forward swim, and backpaddle. Following spinal cord transection, rostral, pocket, and caudal scratches can be evoked by mechanical stimulation of the shell. Comparisons of the kinematics and motor patterns of these six behaviors provide insights regarding neuronal mechanisms underlying their production. All six behaviors were characterized by alternating hip flexion and extension and by an event during which force was exerted against a substrate. The portion of the cycle occupied by hip flexion or extension movement varied across behaviors. Hip extension occupied well over half the cycle period in the forward step and the caudal scratch. The cycle was split into approximately half hip flexion and half hip extension for the forward swim, the backpaddle, and the rostral scratch. Hip flexion occupied over half the cycle in the pocket scratch. The swim and scratch forms had curvilinear, crescent-shaped toe trajectories and a single burst of monoarticular knee extensor activity during each cycle. The forward step had a linear toe trajectory and two bursts of knee extensor activity during each cycle, one during swing and one during stance. Timing of monoarticular knee extensor onset was similar for: the forward swim, the rostral scratch, and the swing phase burst of forward step; the pocket scratch and the stance phase burst of forward step; and the backpaddle and the caudal scratch. Amplitudes of muscle activity varied among the six behaviors; high amplitudes of activity were associated with events during which force was exerted against a substrate. These times of force exertion were: stance phase in the forward step, powerstroke in the forward swim and the backpaddle, and rubs of the limb against the shell in the scratch forms. The six behaviors studied represent a range of parameter values, as evidenced by relative durations of hip flexion to hip extension, knee extensor phasing, and electromyogram (EMG) amplitudes. This range of behaviors could be produced by assembling different combinations of neurons from a common pool, with all six behaviors likely sharing some basic circuitry. The extent of shared circuitry may be greater between behaviors with similar timing, e.g., backpaddle and caudal scratch.

Expanding your perioperative practice into the health care industry.

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Scratch-swim hybrids in the spinal turtle: blending of rostral scratch and forward swim.

Turtles with a complete transection of the spinal cord just posterior to the forelimb enlargement at the D2-D3 segmental border produced coordinated rhythmic hindlimb movements. Ipsilateral stimulation of cutaneous afferents in the midbody shell bridge evoked a rostral scratch. Electrical stimulation of the contralateral dorsolateral funiculus (DLF) at the anterior cut face of the D3 segment activated a forward swim. Simultaneous stimulation of the ipsilateral shell bridge and the contralateral DLF elicited a scratch-swim hybrid: a behavior that blended features of both rostral scratch and forward swim into each cycle of rhythmic movement. This is the first demonstration of a scratch-locomotion hybrid in a spinal vertebrate. The rostral scratch and the forward swim shared some characteristics: alternating hip flexion and extension, similar timing of knee extensor activity within the hip cycle, and a behavioral event during which force was exerted against a substrate. During each cycle, each behavior exhibited three sequential stages, preevent, event, and postevent. The rostral scratch event was a rub of the foot against the stimulated shell site. The forward swim event was a powerstroke, a hip extension movement with the foot held in a vertical position with toes and webbing spread. The two behaviors differed with respect to several features: amount of hip flexion and extension, electromyogram (EMG) amplitudes, and EMG duty cycles. Scratch-swim hybrids displayed two events, the scratch rub and the swim powerstroke, within each cycle. Hybrid hip flexion excursion, knee extensor EMGs, and hip flexor EMGs were similar to those of the scratch; hybrid hip extension excursion and hip extensor EMGs were similar to those of the swim. The hybrid also had three sequential stages during each cycle: 1) a combined scratch prerub and swim postpowerstroke, 2) a scratch rub that also served as a swim prepowerstroke, and 3) a swim powerstroke that also served as a scratch postrub. Merging of the rostral scratch with the forward swim was possible because of similarities between the sequential stages of the two forms, making them biomechanically compatible for hybrid formation. Kinematic and myographic similarities between the rostral scratch and the forward swim support the hypothesis that the two behaviors share common neural circuitry. The common features of the sequential stages of each behavior and the production of scratch-swim hybrids provide additional support for the hypothesis of a shared core of spinal cord neurons common to both rostral scratch and forward swim.

Central pattern generators and interphyletic awareness.

Our understandings of how neuronal networks organized as central pattern generators generate motor behavior have greatly increased in the last 40 years. In the 60s, many investigators studying invertebrate motor behaviors were not aware of the work of those studying vertebrate motor behaviors, and vice versa. In the 70s, key conferences provided venues for important interactions among investigators working on preparations in different species. These interactions, termed interphyletic awareness, continued in the 80s and 90s at major conferences and played important roles in the development of our understandings of central pattern generators for motor behavior in these decades.

Example of 2:1 interlimb coordination during fictive rostral scratching in a spinal turtle.

The usual interlimb coordination pattern during fictive rostral scratching in turtles is 1:1 coordination. We describe an example in a turtle of 2:1 coordination during fictive rostral scratching in which there were two cycles of ipsilateral hip flexor activity during each cycle of contralateral hip extensor activity. During 2:1 coordination, there were fluctuations in the ipsilateral hip flexor cycle period such that a larger ipsilateral hip flexor normalized period, which was associated with the onset of a contralateral hip extensor burst, alternated with a smaller ipsilateral hip flexor normalized period, which was associated with the absence of the onset of a contralateral hip extensor burst. These observations support the concept that contralateral circuitry modulates the timing of ipsilateral motor rhythms and therefore contributes to the production of the ipsilateral motor pattern for rostral scratching.

Reconstruction of flexor/extensor alternation during fictive rostral scratching by two-site stimulation in the spinal turtle with a transverse spinal hemisection.

Analyses of fictive scratching motor patterns in the spinal turtle with transverse hemisection provided support for the concept of bilateral shared spinal cord circuitry among neurons responsible for generating left- and right-side rostral, pocket, and caudal fictive scratching. Rhythmic bursts of hip flexor activity, the hip extensor deletion variation of fictive rostral scratching, were elicited by ipsilateral stimulation in the rostral scratch receptive field of a spinal turtle [transection at the segmental border between the second (D2) and third (D3) postcervical spinal segments] with a contralateral transverse hemisection one segment anterior to the hindlimb enlargement (at the D6-D7 segmental border). In addition, other sites were stimulated in this preparation: (1) contralateral sites in a rostral, pocket, or caudal scratch receptive field or (2) ipsilateral sites in a caudal scratch receptive field. A reconstructed fictive rostral scratch motor pattern of rhythmic alternation between hip flexor and hip extensor activation was produced by simultaneous stimulation of one site in the ipsilateral rostral scratch receptive field and another site in one of the other scratch receptive fields. This reconstructed rostral scratch motor pattern resembled the normal rostral scratch motor pattern produced by one-site rostral scratch stimulation of a spinal turtle (D2-D3 transection) with no additional transections. The observation of a reconstructed rostral scratch motor pattern produced by two-site stimulation in the spinal turtle with transverse hemisection supports the concept that hip extensor circuitry activated by stimulation of other scratch receptive fields is shared with circuitry activated by ipsilateral rostral scratch receptive field stimulation.

Spinal motor patterns in the turtle.

Rhythmic alternation between ipsilateral hip flexors and extensors occurs during the normal pattern of fictive rostral scratching in response to unilateral midbody stimulation in D3-end turtles (complete spinal transection posterior to the forelimb enlargement). Unilateral midbody stimulation evokes rhythmic bursts of ipsilateral hip flexor activity with no hip extensor activity in D3-end turtles with D6-D7 contralateral hemisection (transverse hemisection anterior to the hindlimb enlargement). Bilateral midbody stimulation in these turtles evokes reconstruction of rhythmic alternation between intact side hip flexors and extensors. These normal motor patterns in response to two-site stimulation are reconstructed because one-site stimulation in this preparation activates only hip flexor rhythms (J. Neurosci. 18: 467). Hip flexor rhythms can therefore occur without hip extensor activation. This supports the concept that reciprocal inhibition between flexor and extensor interneurons is not required for flexor motor rhythm generation. Reciprocal inhibition, when present, also contributes to rhythmicity (J. Neurophysiol. 78: 3479; see also Currie and Gonsalves, this volume). Both mechanisms for rhythmicity are included in the Grillner unit burst generator model: hip flexor unit burst generators may be rhythmogenic in the absence of hip extensor activity and reciprocal inhibition contributes to rhythmogenesis. Contralateral midbody stimulation assisted in the activation of ipsilateral hip extensor rhythmicity during reconstructed rostral scratching. This result provides additional support for the hypothesis that a bilateral shared core of hip interneuronal circuitry plays a critical role in the generation of the normal pattern of fictive rostral scratching (J. Neurosci. 15: 4343).

Spinal cord coordination of hindlimb movements in the turtle: intralimb temporal relationships during scratching and swimming.

Spinal cord neuronal circuits generate motor neuron activity patterns responsible for rhythmic hindlimb behaviors such as scratching and swimming. Kinematic analyses of limb movements generated by this motor neuron output reveal important characteristics of these behaviors. Intralimb kinematics of the turtle hindlimb were characterized during five distinct rhythmic forms of behavior: three forms of scratching and two forms of swimming. In each movement cycle for each form, the angles of the hip and knee joints were measured as well as the timing of a behavioral event, e.g., rub onset in scratching or powerstroke onset in swimming. There were distinct differences between the kinematics of different forms of the same behavior, e.g., rostral scratch versus pocket scratch. In contrast, there were striking similarities between forms of different behaviors, e.g., rostral scratch versus forward swimming. For each form of behavior there was a characteristic angular position of the hip at the onset of each behavioral event (rub or powerstroke). The phase of the onset of knee extension within the hip position cycle occurred while the hip was flexing in the rostral scratch and forward swim and while the hip was extending in the pocket scratch, caudal scratch, and back-paddling form of swimming. The phase of the onset of the behavioral event was not statistically different between rostral scratch and forward swim; nor was it different between pocket scratch and caudal scratch. These observations of similarities at the movement level support the suggestion that further similarities, such as shared spinal circuitry, may be present at the neural circuitry level as well.

Spinal cord coordination of hindlimb movements in the turtle: interlimb temporal relationships during bilateral scratching and swimming.

Hindlimb interlimb coordination was examined in turtles during symmetrical "same-form" behaviors in which both hindlimbs utilized the same movement strategy ("form") and during asymmetric "mixed-form" behaviors in which the form exhibited by one hindlimb differed from that of its contralateral partner. In spinal turtles, three forms of scratching were examined: rostral, pocket, and caudal. Bilateral symmetrical same-form scratching was studied for each of the forms. Asymmetric mixed-form scratching (rostral scratching of a hindlimb and pocket scratching of the other hindlimb) was also examined. In intact turtles, two forms of swimming were examined: forward swimming and back-paddling. The symmetrical behavior of bilateral forward same-form swimming and the asymmetric behavior of turning mixed-form swimming (forward swimming of 1 hindlimb and back-paddling of the other hindlimb) were studied. For all behaviors examined, most episodes displayed absolute or 1:1 coordination; in this type of coordination, during each movement cycle that began and ended with the onset of ipsilateral hip flexion, there was a single onset of contralateral hip flexion. For most of these episodes there was out-of-phase coordination between hip movements; the onset of contralateral hip flexion occurred near the onset of ipsilateral hip extension midway through the ipsilateral movement cycle. Bilateral caudal/caudal same-form scratching displayed out-of-phase 1:1 coordination during some episodes and in-phase 1:1 coordination during other episodes. During in-phase coordination, the onset of contralateral hip flexion occurred near the onset of ipsilateral hip flexion close to the start of the ipsilateral movement cycle. In a few cases of bilateral same-form scratching there were episodes of relative or 2:1 coordination; in this type of coordination, during each movement cycle of the slowly moving limb that began and ended with ipsilateral hip flexion, there were two distinct occurrences of the onset of contralateral hip flexion. The observation that out-of-phase movements of the hip occurred during symmetrical as well as asymmetric behaviors is consistent with the hypothesis that timing signals related to hip movement play a major role in interlimb phase control. The neural mechanisms responsible for interlimb phase control are not well understood in vertebrates. The present demonstration of bilateral scratching in spinal turtles suggests that this preparation may be suitable for additional experiments to examine mechanisms of vertebrate interlimb phase control.

Bilateral control of hindlimb scratching in the spinal turtle: contralateral spinal circuitry contributes to the normal ipsilateral motor pattern of fictive rostral scratching.

In a spinal turtle, unilateral stimulation in the rostral scratch receptive field elicited rhythmic fictive rostral scratching in ipsilateral hindlimb motor neurons; contralateral hip motor activity was also rhythmic and out-of-phase with ipsilateral hip motor activity. When left and right rostral scratch receptive fields were stimulated simultaneously, bilateral rhythmic fictive rostral scratching was produced; left hindlimb scratching was out-of-phase with right hindlimb scratching. Thus, spinal circuits coordinate interlimb phase during bilateral fictive scratching. We examined the contributions of contralateral spinal circuitry to the normal pattern of right hindlimb fictive rostral scratching by removing the left halves of the D7 segment and the hindlimb enlargement (D8-S2 segments). After left-hemicord removal, stimulation in the right rostral scratch receptive field usually elicited a variation of rostral scratching with rhythmic right hip flexor activity and no right hip extensor activity; thus, right hip flexor rhythm generation does not require left hindlimb enlargement circuitry. Normal right hindlimb rostral scratching with rhythmic alternation between hip flexor and extensor activities was rarely observed; thus, contralateral spinal circuitry contributes to the production of normal ipsilateral fictive rostral scratching. After left-hemicord removal, stimulation in the left rostral scratch receptive field elicited rhythmic right hip extensor activity; thus, contralateral spinal circuitry can generate a hip extensor rhythm during ipsilateral rostral scratch receptive field stimulation. Our observations and those of Berkowitz and Stein (1994a,b) support the concept that an ipsilateral hindlimb's normal rostral scratch motor pattern is generated by a modular central pattern generator that is bilaterally distributed in the spinal cord.

Activity of descending propriospinal axons in the turtle hindlimb enlargement during two forms of fictive scratching: broad tuning to regions of the body surface.

We recorded the activity of descending propriospinal axons at the caudal end of a seven-segment (D3-D9) turtle spinal cord preparation. These seven spinal segments contain sufficient neural circuitry to select and generate fictive rostral scratching or fictive pocket scratching in response to tactile stimulation in the appropriate region of the body surface. Each turtle received two spinal transections, one just caudal to the forelimb enlargement and one in the middle of the hindlimb enlargement. Descending propriospinal axons were recorded extracellularly from the hindlimb enlargement on one side of the body, while the ipsilateral or contralateral body surface was stimulated. Concurrent recordings were made from ipsilateral and contralateral hindlimb muscle nerves to monitor fictive scratch motor patterns. We found that most tactilely responsive descending propriospinal axons were excited by stimulation anywhere within the rostral scratch or pocket scratch receptive fields on at least one side of the body, and often on both sides. The activity of these neurons was usually rhythmically modulated during fictive rostral scratching and fictive pocket scratching. Many neurons with large excitatory receptive fields generated action potentials at their highest rate during stimulation of a particular region of the body surface on one side, and generated action potentials at progressively lower rates during stimulation of sites progressively farther away. Thus, these units were broadly tuned to a region of the body surface. Some were tuned to a region of the rostral scratch receptive field and others were tuned to a region of the pocket scratch receptive field. These data suggest that selection of the appropriate form of scratching, rostral or pocket, may be mediated by populations of broadly tuned neurons rather than by highly specialized neurons.

Activity of descending propriospinal axons in the turtle hindlimb enlargement during two forms of fictive scratching: phase analyses.

In the preceding companion article (Berkowitz and Stein, 1994b), we showed that many descending propriospinal neurons in the turtle were rhythmically activated during two different motor patterns, fictive rostral scratching and fictive pocket scratching. In this article, we present phase analyses of the activity of each such neuron during fictive scratching. Each neuron's activity was concentrated in a particular phase of the ipsilateral hip flexor muscle nerve (VP-HP) activity cycle; each had a distinct "preferred phase." Each neuron's preferred phase during fictive rostral scratching was similar to its preferred phase during fictive pocket scratching. This result is consistent with the idea that some descending propriospinal neurons may contribute to the generation of both rostral scratching and pocket scratching. Many descending propriospinal neurons were rhythmically activated during fictive scratching evoked on either side of the body. This activity may contribute to production of bilateral hindlimb movements during scratching. It is also possible that synaptic interactions between the two sides of the spinal cord may be important in generating the motor patterns for movement of a single hindlimb. In addition, we present a model which illustrates that a population of propriospinal neurons, each of which is broadly tuned to a region of the body surface and is rhythmically activated in a constant phase of the hip control cycle, could mediate the selection and generation of rostral scratching and pocket scratching. Thus, the selection of an appropriate motor pattern and the production of the required knee-hip synergy may each be distributed over a diverse population of spinal cord neurons. This model requires that each such neuron project to both knee muscle and hip muscle motoneurons. According to this model, the process of selecting a motor pattern would not be completed until knee muscle motoneurons integrate overlapping excitatory and inhibitory inputs.

Descending propriospinal axons in the hindlimb enlargement of the red-eared turtle: cells of origin and funicular courses.

Spinal neurons with descending axons are important components of spinal sensorimotor networks. We used an anatomical tracing technique to study the distribution of descending propriospinal axons and cell bodies in red-eared turtles. We injected horseradish peroxidase into a portion of one funiculus in the middle of the hindlimb enlargement and examined six spinal segments rostral to the injection site (dorsal 3 through dorsal 8) for labeled neuronal cell bodies. Injections into each region of the white matter labeled substantial numbers of descending propriospinal neurons. Each injection labeled cell bodies over most of the six spinal segments examined. Each injection also labeled cell bodies in the ipsilateral dorsal horn, intermediate zone, and ventral horn as well as the contralateral intermediate zone and ventral horn. Injections into each of four regions of the white matter, the dorsal funiculus, the medial part of the lateral funiculus, the lateral part of the lateral funiculus, and the ventral funiculus reliably gave rise to a distinct distribution of labeled cell bodies. These experiments establish that descending propriospinal axons in red-eared turtles are found in all regions of the spinal white matter. This finding contrasts with a popular contemporary view of the organization of descending propriospinal axons in mammals. These experiments also demonstrate that neurons in each region of the gray matter give rise to a different distribution of descending, funicular axons, although these distributions are widely overlapping. Different funicular axon distributions could be associated with different sets of synaptic contacts with the white-matter dendrites of spinal neurons.

The role of NMDA receptors in information processing.

In this review, we have concentrated on the parallels between the cellular properties of the NMDA receptor and a variety of functional properties within sensory and motor systems. Of course, the NMDA channel exists within the cell in conjunction with a variety of other channels, including non-NMDA channels. Although the NMDA receptor is unique in a cellular sense--it is the only ligand-gated channel that is also voltage dependent and calcium permeable--it is not unique in a functional sense. A cell that has non-NMDA receptors and voltage-sensitive channels will also exhibit nonlinear behavior. Moreover, Buhrle & Sonnhof (1983) demonstrated some time ago that calcium flows into frog motor neurons through more than one type of calcium channel. The contribution to the inflow of calcium from NMDA channels may vary from cell to cell and could easily be a minor proportion of the total. Many authors have pointed out that the NMDA channel has a low conductance at a resting potential of -70 mV. However, many cells in the nervous system are depolarized from -70 mV by excitatory input. Thus, as pointed out above. NMDA receptors make a contribution to the tonic or spontaneous activity of cells in both visual cortex and spinal cord. In practice, many cells are probably working in a range of membrane potentials where the NMDA channels are always open to some extent. Even in the hippocampal slice where a substantial amount of afferent input is removed, NMDA receptors contribute to spontaneous activity (Sah et al 1989). Does the NMDA receptor act as a switch? Does it act as an AND gate? The suggestion that it may act as a switch comes from work on LTP in the hippocampus, which is readily produced by high-frequency stimulation and is abolished by APV. However, activation of the NMDA receptor is only the first in a sequence of reactions leading to LTP: In theory, switch-like behavior could also be produced by calcium-buffering systems within dendritic spines, or by enzymatic processes (Lisman 1985; Zador et al 1990). Fox & Daw (1992) have modeled the action of NMDA and non-NMDA receptors that are activated in parallel with each other, and shown that the occurrence of switch-like behavior depends on the relative density of NMDA versus non-NMDA receptors. Switch-like behavior is not seen in the visual cortex, but might be seen in the hippocampus if the relative density of NMDA receptors there was higher than in the visual cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

Glutamate antagonists applied to midbody spinal cord segments reduce the excitability of the fictive rostral scratch reflex in the turtle.

Glutamate antagonists applied to the cutaneous-processing region of the rostral scratch circuit in turtles reduced the excitability of the rostral scratch reflex. Segments D3-D6 (D3 = 3rd postcervical) of the midbody spinal cord receive cutaneous afferents from the rostral scratch receptive field and perform the initial integration of this cutaneous sensory input. These cutaneous-processing segments are located anterior to the rostral scratch motor pattern generator that resides mainly in segments D7-D10 located in and near the hindlimb enlargement. We prepared 1 or 2 of the midbody segments for bath application of glutamate antagonists in preparations with a complete transection of the spinal cord anterior to segment D3. Each preparation was immobilized by neuromuscular blockade and fictive scratch motor output was recorded from hindlimb muscle nerves. Application of the NMDA N-methyl-D-aspartate) antagonist APV (D-2-amino-5-phosphonovaleric acid, 50 microM) to a midbody segment significantly reduced the motor burst frequency of rostral scratch responses evoked by 3-Hz electrical stimulation of a site in that segment's dermatome. These data suggest that NMDA receptors contribute to cutaneous processing in the rostral scratch circuit. Application of APV to a midbody segment also reduced the magnitude of temporal summation in the scratch circuit in response to electrical stimuli delivered to the shell at 4- to 5-s intervals. Temporal summation was monitored at the level of hindlimb motor output as well as at the level of unit activity from 'long-afterdischarge' neurons in the midbody segments. Our observations are consistent with the hypothesis that NMDA receptors contribute to the prolonged activation of 'long-afterdischarge' neurons and the multisecond storage of excitation in the scratch reflex pathway.