Biology subjects

Ketzef, M.

Publications and source records attributed to Ketzef, M..

3 recordsLinked to original sources

bioRxiv2022

Sensory responses in dorsolateral striatum are modulated by motor activity in a dopamine-dependent manner

The dorsolateral striatum (DLS) receives excitatory inputs from both sensory and motor cortical regions and is involved in sensory and motor functions. In cortical regions, sensory responses are altered by motor activity, however, it is not known if such sensorimotor interactions also occur in the striatum and how they are modulated by dopamine (DA). To determine the impact of motor activity on striatal sensory processing, we performed in vivo whole-cell recordings in the DLS of awake mice during the presentation of tactile stimuli. Striatal medium spiny neurons (MSNs) were activated by both whisker stimulation and spontaneous whisking, however, responses to whisker deflection during ongoing whisking were attenuated. DA depletion reduced the representation of whisking in direct-pathway MSNs, but not in those of the indirect-pathway. Furthermore, DA depletion impaired the discrimination between ipsi- and contralateral sensory stimulation in both direct- and indirect- pathway MSNs. Our results show that sensory responses in basal ganglia circuits are modulated by motor activity and that both processes are dopamine- and cell type-dependent.

neuroscience↗

bioRxiv2020

Differential Synaptic Input to External Globus Pallidus Neuronal Subpopulations In Vivo.

The rodent external Globus Pallidus (GPe) contains two main neuronal subpopulations, prototypic and arkypallidal cells, which differ in their cellular properties. Their functional synaptic connectivity is, however, largely unknown. Here, we studied the membrane properties and synaptic inputs to these subpopulations in the mouse GPe. We obtained in vivo whole-cell recordings from identified GPe neurons and used optogenetic stimulation to dissect their afferent inputs from the striatum and subthalamic nucleus (STN). All GPe neurons received barrages of excitatory and inhibitory input during slow wave activity. The modulation of their activity was cell-type specific and shaped by their respective membrane properties and afferent inputs. Both GPe subpopulations received synaptic input from STN and striatal projection neurons (MSNs). STN and indirect pathway MSNs strongly targeted prototypic cells while direct pathway MSNs selectively inhibited arkypallidal cells. We show that GPe subtypes are differently embedded in the basal ganglia network, supporting distinct functional roles.

neuroscience↗

bioRxiv2019

Direct Pathway Neurons in Mouse Dorsolateral Striatum In Vivo Receive Stronger Synaptic Input than Indirect Pathway Neurons

Striatal projection neurons, the medium spiny neurons (MSNs), play a crucial role in various motor and cognitive functions. MSNs express either D1 or D2 type dopamine receptors and initiate the direct-pathway (dMSNs) or indirect pathways (iMSNs) of the basal ganglia, respectively. dMSNs have been shown to receive more inhibition than iMSNs from intrastriatal sources. Based on these findings, computational modelling of the striatal network has predicted that under healthy conditions dMSNs should receive more excitatory input than iMSNs. To test this prediction, we analyzed in vivo whole-cell recordings from dMSNs and iMSNs in healthy and dopamine-depleted (6OHDA) anaesthetized mice. By comparing their membrane potential fluctuations, we found that dMSNs exhibited considerably larger membrane potential fluctuations over a wide frequency range. Furthermore, by comparing the spike-triggered average membrane potentials, we found that dMSNs depolarized towards the spike threshold significantly faster than iMSNs did. Together, these finding corroborate the theoretical prediction that direct-pathway MSNs receive stronger input than indirect-pathway neurons. Finally, we found that dopamine-depleted mice exhibited no difference between the membrane potential fluctuations of dMSNs and iMSNs. These data provide new insights into the question how a lack of dopamine may lead to behavior deficits associated with Parkinsons disease.\n\nSignificance statementThe direct and indirect pathways of the basal ganglia originate from the D1 and D2 type dopamine receptor expressing medium spiny neurons (dMSNs and iMSNs), respectively. To understand the role of the striatum in brain function and dysfunction it is important to characterize the differences in synaptic inputs to the two MSN types. Theoretical results predicted that dMSNs should receive stronger excitatory input than iMSNs. Here, we studied membrane potential fluctuation statistics of MSNs recorded in vivo in anaesthetized mice and found that dMSNs, indeed, received stronger synaptic input than iMSNs. We corroborated this finding by spike-triggered membrane potential analysis, showing that dMSNs spiking required more synaptic input than iMSNs spiking did, as had been predicted by computational models.

neuroscience↗