Developmental changes in eyeblink conditioning and simple spike activity in the cerebellar cortex

Nicholson, Daniel A.; Freeman, John H.

doi:10.1002/dev.10149

Cited by 21 publications

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References 58 publications

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“…The developmental changes in pontine neuronal activity correspond to developmental changes in CS-elicited neuronal activity in the cerebellar cortex and nuclei Nicholson and Freeman Jr. 2004). As a result of CS pathway development, CS input to the cerebellum in younger rats may not be strong enough to induce synaptic plasticity.…”

Section: Discussionmentioning

confidence: 96%

“…The most substantial developmental change in the US pathway is an increase in the magnitude of cerebellar inhibitory feedback to the inferior olive (Nicholson and Freeman Jr. 2003a,b). The developmental change in inhibitory feedback is due to an increase in inhibitory synapses within the inferior olive (Nicholson and Freeman Jr. 2003a). Developmental addition of inhibitory synapses within the inferior olive results in a decrease in complex spike activity in the cerebellar cortex, which influences the maintenance of synaptic plasticity within the cerebellum.…”

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confidence: 99%

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Pontine stimulation overcomes developmental limitations in the neural mechanisms of eyeblink conditioning

2005

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Pontine neuronal activation during auditory stimuli increases ontogenetically between postnatal days (P) P17 and P24 in rats. Pontine neurons are an essential component of the conditioned stimulus (CS) pathway for eyeblink conditioning, providing mossy fiber input to the cerebellum. Here we examined whether the developmental limitation in pontine responsiveness to a CS in P17 rats could be overcome by direct stimulation of the CS pathway. Eyeblink conditioning was established in infant rats on P17-P18 and P24-P25 using pontine stimulation as a CS. There were no significant age-related differences in the rate or level of conditioning. Eyeblink conditioned responses established with the stimulation CS were abolished by inactivation of the ipsilateral cerebellar nuclei and overlying cortex in both age groups. The findings suggest that developmental changes in the CS pathway play an important role in the ontogeny of eyeblink conditioning.Eyeblink classical conditioning has been used as a model system for examining developmental changes in the neural mechanisms underlying motor learning . It is well established that eyeblink conditioning in adult mammals depends on cerebellar interactions with its afferent and efferent brainstem nuclei (Mauk and Donegan 1997;Christian and Thompson 2003). The cerebellum receives input stimulation from an auditory conditioned stimulus (CS) through the pontine mossy fiber projection (Steinmetz et al. , 1987(Steinmetz et al. , 1989Steinmetz 1990;Steinmetz and Sengelaub 1992;Tracy et al. 1998). Input stimulation from an air puff or face shock unconditioned stimulus (US) reaches the cerebellum through the climbing fiber projection from the inferior olive (McCormick et al. 1985;Mauk et al. 1986;Steinmetz et al. 1989). The convergence of mossy and climbing fiber activation of cerebellar neurons is thought to result in changes in synaptic efficacy that constitute the substrate of learning and drive the production of the eyeblink conditioned response (CR). Cerebellar output produces inhibitory feedback to the inferior olive and excitatory feedback to the pons (Sears and Steinmetz 1991;Clark et al. 1997;Kim et al. 1998;Bao et al. 2000;Medina et al. 2002). The feedback connections are thought to be important for acquisition and maintenance of CRs (Medina et al. 2002).Eyeblink conditioning emerges ontogenetically between postnatal days (P) P17 and P24 in rats (Stanton et al. 1992). Neurophysiological, neuropharmacological, and neuroanatomical analyses of the ontogeny of eyeblink conditioning in rats indicate that the developmental emergence of eyeblink conditioning is due to developmental changes in the CS and US pathways . The most substantial developmental change in the US pathway is an increase in the magnitude of cerebellar inhibitory feedback to the inferior olive (Nicholson and Freeman Jr. 2003a,b). The developmental change in inhibitory feedback is due to an increase in inhibitory synapses within the inferior olive (Nicholson and Freeman Jr. 2003a). Developmental addition of inhibitory syn...

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Section: Discussionmentioning

confidence: 96%

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Pontine stimulation overcomes developmental limitations in the neural mechanisms of eyeblink conditioning

2005

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“…Studies of Pkj firing during trace eyeblink conditioning paradigms have shown both simple monophasic and complex, multiphasic changes in spike output during conditioned stimuli (25,26). These complex changes may be partially due to the mechanisms described in this paper.…”

Section: Discussionmentioning

confidence: 99%

Pattern-dependent, simultaneous plasticity differentially transforms the input-output relationship of a feedforward circuit

Smith

Otis

2005

Proc. Natl. Acad. Sci. U.S.A.

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Memories are believed to be encoded by changes in the synaptic connections between neurons. Although many forms of synaptic plasticity have been identified, it remains unknown how such changes affect local circuits. Feedforward inhibitory networks are a common type of local circuitry and occur when principal neurons and their afferent inhibitory interneurons receive the same input. Using slices of cerebellar cortex, we explored how synaptic plasticity at multiple sites within a feedforward inhibitory network consisting of parallel fibers, interneurons, and Purkinje neurons alters the output of this circuit. We found that stimuli resembling baseline activity potentiated feedforward excitatory and simultaneously depressed feedforward inhibitory pathways. In contrast, stimuli resembling sensory-evoked patterns of firing potentiated both types of feedforward connections. These distinct forms of ensemble plasticity change the way Purkinje neurons subsequently respond to inputs. Such concerted changes in the circuitry of cerebellar cortex may contribute to certain forms of sensorimotor learning.earning and memory in mammalian brains is widely believed to be anchored in long-lasting changes in the strength of synaptic connections between neurons. Despite the identification of dozens of forms of synaptic plasticity, it remains unknown how these phenomena change the response properties of local circuits. We set out to explore how use-dependent changes in synaptic strength within a feedforward circuit affect the transformation from input to output.Feedforward inhibition is a common configuration for local circuitry incident on principal neurons. In such circuits, a common excitatory pathway synapses on both principal neurons and their afferent inhibitory interneurons (IN). This situation occurs in the cerebral (1) and cerebellar cortices (2), hippocampus (3), thalamus (4), and other brain areas (5, 6). In the cerebellar cortex, granule cell axons bifurcate in the molecular layer to form parallel fibers (PFs). These excitatory inputs synapse on Purkinje (Pkj) neurons and their afferent molecular layer interneurons (Fig. 1A).Within this simple cerebellar circuit, different forms of synaptic plasticity have been described at various synapses. We explored how multiple types of synaptic plasticity occurring at the same time, hereafter called ''simultaneous plasticity,'' leads to differential changes in the input-output relationship of the feedforward inhibitory circuit in response to realistic conditioning activity. Because Pkjs fire spontaneously (7,8), spike outputs in response to inputs are superimposed on a high rate of background activity. This mechanism enables the circuit to reflect changes in inhibition as well as excitation (9). We show that patterns of conditioning activity that resemble baseline firing cause potentiation of direct PF input to Pkjs and depression of PF input to INs, resulting in a potentiation of spike output. In contrast, patterns of conditioning activity that resemble responses to sensory stimuli p...

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“…Simple spikes were recorded using the same experimental techniques as the Freeman and Nicholson (2000) study. Stimulus-evoked and learning-related modulation of Purkinje cell simple spike activity from eye regions within lobule HVI emerged ontogenetically in parallel with eyeblink conditioning (Nicholson & Freeman, 2004). During paired CS-US training, the proportion of simple spikes that showed learning-specific increases or decreases in activity increased with age.…”

Section: Development Of Cerebellar Learning Mechanismsmentioning

confidence: 91%

“…In addition to developmental changes in the frequency and magnitude of learning-specific neuronal activity in the cerebellum, there was a substantial developmental increase in the magnitude of neuronal responses to the CS and US Nicholson & Freeman, 2004). The ontogenetic increase in the cerebellar response to the US suggests that the neural pathway that conducts US stimulation to the cerebellum or the synaptic connections between the US pathway and cerebellar neurons undergoes substantial developmental change postnatally.…”

Section: Us Pathway Developmentmentioning

confidence: 99%

Developmental Changes in the Neural Mechanisms of Eyeblink Conditioning

Freeman

Nicholson²

2004

Behavioral and Cognitive Neuroscience Reviews

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Eyeblink conditioning has been used as a model system for examining the ontogeny of associative learning and its neural basis in rodents. Associative eyeblink conditioning emerges between postnatal days (P) 17 and 24 in rats. Neurophysiological studies in infant rats during eyeblink conditioning revealed developmental changes in the activity of cerebellar neurons that correspond to the ontogenetic emergence of eyeblink conditioning. The developmental changes in cerebellar neuronal activity suggest that the ontogeny of eyeblink conditioning is related to changes in learning mechanisms rather than motor performance mechanisms. Additional neurophysiological and neuroanatomical studies demonstrated that the developmental changes in neuronal activity in the cerebellum are due to developmental changes in interactions between the cerebellum and its inputs, the inferior olive and pontine nuclei. Developmental changes in cerebellar inputs and regulation of its inputs affect the induction of learning-related plasticity, thereby affecting the rate and magnitude of conditioning.

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Developmental changes in eyeblink conditioning and simple spike activity in the cerebellar cortex

Cited by 21 publications

References 58 publications

Pontine stimulation overcomes developmental limitations in the neural mechanisms of eyeblink conditioning

Pontine stimulation overcomes developmental limitations in the neural mechanisms of eyeblink conditioning

Pattern-dependent, simultaneous plasticity differentially transforms the input-output relationship of a feedforward circuit

Developmental Changes in the Neural Mechanisms of Eyeblink Conditioning

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