Morphological Correlates of Intrinsic Electrical Excitability in Neurons of the Deep Cerebellar Nuclei

Abstract

phological correlates of intrinsic electrical excitability in neurons of the deep cerebellar nuclei. J Neurophysiol 89: 1738 -1747, 2003; 10.1152/jn.01043.2002. To what degree does neuronal morphology determine or correlate with intrinsic electrical properties within a particular class of neuron? This question has been examined using microelectrode recordings and subsequent neurobiotin filling and reconstruction of neurons in the deep cerebellar nuclei (DCN) of brain slices from young rats (P13-16). The neurons reconstructed from these recordings were mostly large and multipolar (17/21 cells) and were likely to represent glutamatergic projection neurons. Within this class, there was considerable variation in intrinsic electrical properties and cellular morphology. Remarkably, in a correlation matrix of 18 electrophysiological and 6 morphological measures, only one morphological characteristic was predictive of intrinsic excitability: neurons with more spines had a significantly slower basal firing rate. To address the possibility that neurons with fewer spines represented a slowly maturing subgroup, recordings and reconstructions were also made from neurons at a younger age (P6 -9). While P6 -9 neurons were morphologically indistinguishable from P13 to 16 neurons, they were considerably less excitable: P6 -9 neurons had a lower spontaneous spiking rate, larger fast AHPs, higher resting membrane potentials, and smaller rebound depolarizations. Thus while the large projection neurons of the DCN are morphologically mature by P6 -9, they continue to mature electrophysiologically through P13-16 in a way that renders them more responsive to the burst-and-pause pattern that characterizes Purkinje cell inhibitory synaptic drive. I N T R O D U C T I O NThe deep cerebellar nuclei (DCN) are at the center of the cerebellar circuitry and form its primary output structure. In the DCN, a variety of excitatory and inhibitory projections, representing several streams of sensory-motor information, converge. Purkinje cells, which constitute the sole output of the cerebellar cortex, send GABAergic inhibitory projections to the DCN. Additionally, the DCN receive glutamatergic excitatory inputs from various precerebellar nuclei and the inferior olive via mossy fibers and climbing fibers, respectively. The firing patterns of the DCN neurons will therefore reflect the sum of all the neural computations that are performed in the cerebellar system that are then translated into a variety of motor outputs. There is increasing evidence that the DCN and an analogous structure, the vestibular nuclei, play an important role in several types of motor learning, including associative eyelid conditioning and adaptation of the vestibulo-ocular re-

Correlations in ion channel expression emerge from homeostatic tuning rules

“…These studies triggered a host of experimental studies that are consistent with the idea that nervous systems must balance the mechanisms that allow them to be plastic with others that maintain their stability (5,40,41,43). Subsequently, both theoretical and experimental studies showed that there are multiple solutions consistent with very similar activity patterns (31,37,(44)(45)(46)(47). It is important to recognize that homeostatic tuning rules, such as those studied here, do not invariably produce the same set of channel densities, but instead result in a target activity that is consistent with a range of solutions.…”

Long-Term Depression at the Mossy Fiber–Deep Cerebellar Nucleus Synapse

“…Large glutamatergic neurons project to the premotor nuclei, medium-to-large GABAergic neurons project to the inferior olive, and small GABAergic and/or glycinergic interneurons project their axons locally, although some have claimed that the local projections are collaterals of GABAergic axons that innervate the olive (Batini et al, 1992;De Zeeuw and Berrebi, 1995). In the present study, we performed whole-cell patch recordings from neurons with somatic diameter larger than 20 m. Hence, the majority of neurons in the present study are presumably glutamatergic projection neurons (Batini et al, 1992;De Zeeuw and Berrebi, 1995;Aizenman et al, 2003). In addition to the glutamatergic projection neurons, it will also be interesting to investigate whether the mossy fiber synapses onto inhibitory neurons in the DCN can also express LTD or LTP.…”

“…The position of the interpositus nuclei was identified in the slices using a 5ϫ objective mounted on an upright microscope (Axioskop 2 FS; Zeiss, Oberkochen, Germany), and DCN neuron somata were then visualized through a 40ϫ water immersion objective using infrared differential interference contrast optics. In the present study, recordings were made from large neurons with somatic diameter larger than 20 m, most of which are thought to correspond to the glutamatergic projection neurons of the cerebellar nuclei (Batini et al, 1992;De Zeeuw and Berrebi, 1995;Aizenman et al, 2003). It is possible, however, that a small number of our recordings were from the largest of the DCN GABAergic inhibitory projection neurons.…”

Rescue of Motor Coordination by Purkinje Cell-Targeted Restoration of Kv3.3 Channels inKcnc3-Null Mice RequiresKcnc1

“…3A-C). Glutamatergic projection neurons were evidenced by their large size (Chan-Palay, 1977;Kumoi et al, 1988;Batini et al, 1992;Aizenman et al, 2003). In contrast to other brain areas in the DCN, it is the large neurons that are relatively fast spiking (Uusisaari et al, 2007).…”