In Vivo Analysis of Inhibitory Synaptic Inputs and Rebounds in Deep Cerebellar Nuclear Neurons

Abstract

Neuronal function depends on the properties of the synaptic inputs the neuron receive and on its intrinsic responsive properties. However, the conditions for synaptic integration and activation of intrinsic responses may to a large extent depend on the level of background synaptic input. In this respect, the deep cerebellar nuclear (DCN) neurons are of particular interest: they feature a massive background synaptic input and an intrinsic, postinhibitory rebound depolarization with profound effects on the synaptic integration. Using in vivo whole cell patch clamp recordings from DCN cells in the cat, we find that the background of Purkinje cell input provides a tonic inhibitory synaptic noise in the DCN cell. Under these conditions, individual Purkinje cells appear to have a near negligible influence on the DCN cell and clear-cut rebounds are difficult to induce. Peripheral input that drives the simple spike output of the afferent PCs to the DCN cell generates a relatively strong DCN cell inhibition, but do not induce rebounds. In contrast, synchronized climbing fiber activation, which leads to a synchronized input from a large number of Purkinje cells, can induce profound rebound responses. In light of what is known about climbing fiber activation under behaviour, the present findings suggest that DCN cell rebound responses may be an unusual event. Our results also suggest that cortical modulation of DCN cell output require a substantial co-modulation of a large proportion of the PCs that innervate the cell, which is a possible rationale for the existence of the cerebellar microcomplex.

Maturation of membrane properties of neurons in the rat deep cerebellar nuclei

“…Rebound spiking, another intrinsic property of DCN neurons, is regarded as encoding the amplitude of inhibitory synapses in cerebellar circuit and serving to transfer inhibitory signals (Pedroarena, 2010). Interestingly, AHP increases were also seen in rebound spikes from post-weaning rats, which suggests maturation of synaptic inputs especially the inhibitory inputs (Waters et al, 2006) may be required for associative cerebellar learning (Bengtsson et al, 2011; Person and Raman, 2012; Witter et al, 2013). …”

“…In addition, there was an increase in AHP amplitude – an index of membrane excitability shown to be important for classical conditioning (Coulter et al, 1989; Schreurs et al, 1998; Wang and Schreurs, 2010) which was accompanied by a prolonged S1S2 interval. Interestingly, an increased AHP amplitude was also observed for the hyperpolarization-elicited rebound spikes, which are modulated by synaptic inputs on DCN especially inputs from Purkinje cells and climbing fibers (Aizenman and Linden, 1999; Bengtsson et al, 2011; Person and Raman, 2012; Zheng and Raman, 2010) and define the accuracy and timing of cerebellar motor performance (Witter et al, 2013). Taken together, these developmental changes represent the maturation of membrane properties of rat DCN neurons and may help explain the enhanced acquisition of conditioned eyeblink responses at this specific period (Freeman, Jr. et al, 1995; Freeman, Jr. and Nicholson, 2004).…”

“…Deep cerebellar nuclei (DCN), the sole non-vestibular output from the cerebellum and an essential component of this neural circuitry, are critical to the ontogeny of eyeblink conditioned responses and have also been a target area for exploring learning-related synaptic plasticity of both excitatory (Aizenman and Linden, 2000; Pugh and Raman, 2006; Pugh and Raman, 2008) and inhibitory inputs (Bengtsson et al, 2011; Pugh and Raman, 2005; Pugh and Raman, 2008; Witter et al, 2013). Studies in developing rats have shown significant anatomical and functional changes in DCN during the first few postnatal weeks (Freeman, Jr. and Nicholson, 2000; Heinsen, 1977; Nicholson and Freeman, Jr., 2004), and thus, anatomical and functional maturation of DCN may influence the process of associative learning and memory by regulating the induction and maintenance of learning-specific changes within DCN (Freeman, Jr. et al, 1995; Freeman, Jr. and Nicholson, 2004).…”

Clusters of cerebellar Purkinje cells control their afferent climbing fiber discharge

“…Anesthesia might alter physiological properties of CN neurons. However, recent studies (25,32) have demonstrated that rebound excitation in CN neurons requires the extensive activation of the presynaptic PCs. Thus, a more likely interpretation is that our protocol of illumination leads to poorly synchronized PC discharges and/or fails to recruit enough presynaptic PCs.…”

Cerebellum and Cerebellar Connections

“…These may be especially prominent after climbing fiberinduced synchronous discharge of complex spike firing of a population of Purkinje cells (Hoebeek et al, 2011). To what extent this rebound firing has a functional characteristic is still a matter of debate (Alvina et al, 2008;Bengtsson et al, 2011;Hoebeek et al, 2011). Even less is known on the responses to Purkinje cell activity of the other populations of cerebellar neurons (Uusisaari and De Schutter, 2011;Uusisaari and Knopfel, 2011).…”