Between in and out: linking morphology and physiology of cerebellar cortical interneurons

Inhibitory synapses display a great diversity through varying combinations of presynaptic GABA and glycine release and postsynaptic expression of GABA and glycine receptor subtypes. We hypothesized that increased flexibility offered by this dual transmitter system might serve to tune the inhibitory phenotype to the properties of afferent excitatory synaptic inputs in individual cells. Vestibulocerebellar unipolar brush cells (UBC) receive a single glutamatergic synapse from a mossy fiber (MF), which makes them an ideal model to study excitatory-inhibitory interactions. We examined the functional phenotypes of mixed inhibitory synapses formed by Golgi interneurons onto UBCs in rat slices. We show that glycinergic IPSCs are present in all cells. An additional GABAergic component of large amplitude is only detected in a subpopulation of UBCs. This GABAergic phenotype is strictly anti-correlated with the expression of type II, but not type I, metabotropic glutamate receptors (mGluRs) at the MF synapse. Immunohistochemical stainings and agonist applications show that global UBC expression of glycine and GABA A receptors matches the pharmacological profile of IPSCs. Paired recordings of Golgi cells and UBCs confirm the postsynaptic origin of the inhibitory phenotype, including the slow kinetics of glycinergic components. These results strongly suggest the presence of a functional coregulation of excitatory and inhibitory phenotypes at the single-cell level. We propose that slow glycinergic IPSCs may provide an inhibitory tone, setting the gain of the MF to UBC relay, whereas large and fast GABAergic IPSCs may in addition control spike timing in mGluRII-negative UBCs.

Section: Different Dynamic Properties Of the Gaba And Glycine Componentsmentioning

confidence: 99%

Mixed Inhibitory Synaptic Balance Correlates with Glutamatergic Synaptic Phenotype in Cerebellar Unipolar Brush Cells

Rousseau¹,

Dugué²,

Dumoulin³

et al. 2012

“…Luckily, UBCs have been identified and characterized in juxtacellular labeling studies of Barmack and Yakhnitsa (2008) and Simpson et al (2005). They discharge at highly regular firing rates and hence show narrow ISI histograms, with a wide range of possible median values.…”

Section: Identification Of Golgi Cells and Mossy Fibersmentioning

confidence: 99%

Characteristics of Responses of Golgi Cells and Mossy Fibers to Eye Saccades and Saccadic Adaptation Recorded from the Posterior Vermis of the Cerebellum

Prsa¹,

Dash²,

Catz³

et al. 2009

The anatomical organization of the granular layer of the cerebellum suggests an important function for Golgi cells (GC) in the pathway conveying mossy fiber (MF) afferents to Purkinje cells. Based on such anatomic observations, early proposals have attributed a role in "gain control" for GCs, a function disputed by recent investigations, which assert that GCs instead contribute to oscillatory mechanisms. However, conclusive physiological evidence based on studies of cerebellum-dependent behavior supporting/dismissing the gain control proposition has been lacking as of yet. We addressed the possible function of this interneuron by recording the activity of a large number of both MFs and GCs during saccadic eye movements from the same cortical area of the monkey cerebellum, namely the oculomotor vermis (OMV). Our cellular identification conformed to previously established criteria, mainly to juxtacellular labeling studies correlating physiological parameters with cell morphology. Response patterns of both MFs and GCs were highly heterogeneous. MF discharges correlated linearly with eye saccade metrics and timing, showing directional preference and precise direction tuning. In contrast, GC discharges did not correlate strongly with the metrics or direction of movement. Their discharge properties were also unaffected by motor learning during saccadic adaptation. The OMV therefore receives a barrage of information about eye movements from different oculomotor areas over the MF pathway, which is not reflected in GCs. The unspecificity of GCs has important implications for the intricacies of neuronal processing in the granular layer, clearly discrediting their involvement in gain control and instead suggesting a more secluded role for these interneurons.

“…The only known source of excitation of UBCs is their single giant mossy fiber input, which can be spontaneously active at high frequencies in vivo (Ͼ Ͼ 20 Hz) and is thus likely to drive the complex pattern of activity of UBCs observed in anesthetized and awake animals (Simpson et al, 2005). To understand how UBCs may transcode their synaptic input, we examined the response of UBCs to extracellular stimulation of the mf.…”

Section: Tonic and Burst Firing Of Cerebellar Ubcs In Response To Mosmentioning

confidence: 99%

“…UBCs have been recorded in in vivo conditions only recently. In anesthetized rats, most cells displayed a regular firing pattern, with just a few firing bursts, whereas in awake rabbits, only data from regular firing cells were discussed (Simpson et al, 2005). Whether bursts in UBCs are physiologically relevant is therefore still an open question.…”

Section: Bimodal Excitability Patterns and Physiological Functionsmentioning

confidence: 99%

See 1 more Smart Citation

T-Type and L-Type Ca²⁺Conductances Define and Encode the Bimodal Firing Pattern of Vestibulocerebellar Unipolar Brush Cells

Diana¹,

Otsu²,

Maton³

et al. 2007

Cerebellar unipolar brush cells (UBCs) are glutamatergic interneurons that receive direct input from vestibular afferents in the form of a unique excitatory synapse on their dendritic brush. UBCs constitute independent relay lines for vestibular signals, and their inherent properties most likely determine how vestibular activity is encoded by the cerebellar cortex. We now demonstrate that UBCs are bimodal cells; they can either fire high-frequency bursts of action potentials when stimulated from hyperpolarized potentials or discharge tonically during sustained depolarizations. The two functional states can be triggered by physiological-like activity of the excitatory input and are encoded by distinct Ca 2ϩ -signaling systems. By combining complementary strategies, consisting of molecular and electrophysiological analysis and of ultrafast acousto-optical deflector-based two-photon imaging, we unraveled the identity and the subcellular localization of the Ca 2ϩ conductances activating in each mode. Fast inactivating T-type Ca 2ϩ channels produce low-threshold spikes, which trigger the high-frequency bursts and generate powerful Ca 2ϩ transients in the brush and, to a much lesser extent, in the soma. The tonic firing mode is encoded by a signalization system principally composed of L-type channels. Ca 2ϩ influx during tonic firing produces a linear representation of the spike rate of the cell in the form of a widespread and sustained Ca 2ϩ concentration increase and regulates cellular excitability via BK potassium channels. The bimodal firing pattern of UBCs may underlie different coding strategies of the vestibular input by the cerebellum, thus likely increasing the computational power of this structure.