Abstract
The sparse connectivity within the striatum in vivo makes the investigation of individual corticostriatal synapses very difficult. Most studies of the corticostriatal input have been done using electrical stimulation under conditions where it is hard to identify the precise origin of the cortical input. We have employed an in vitro dissociated cell culture system that allows the identification of individual corticostriatal pairs and have been developing methods to study individual neuron inputs to striatal neurons. In mixed corticostriatal cultures, neurons had resting activity similar to the system in vivo. Up/down states were obvious and seemed to encompass the entire culture. Mixed cultures of cortical neurons from transgenic mice expressing green fluorescent protein with striatal neurons from wild-type mice of the same developmental stage allowed visual identification of individual candidate corticostriatal pairs. Recordings were performed between 12 and 37 days in vitro (DIV). To investigate synaptic connections we recorded from 69 corticostriatal pairs of which 44 were connected in one direction and 25 reciprocally. Of these connections 41 were corticostriatal (nine inhibitory) and 53 striatocortical (all inhibitory). The observed excitatory responses were of variable amplitude (−10 to −370 pA, n = 32). We found the connections very secure – with negligible failures on repeated stimulation (approximately 1 Hz) of the cortical neuron. Inhibitory corticostriatal responses were also observed (−13 to −314 pA, n = 9). Possibly due to the mixed type of culture we found an inhibitory striatocortical response (−14 to −598 pA, n = 53). We are now recording from neurons in separate compartments to more closely emulate neuroanatomical conditions but still with the possibility of the easier identification of the connectivity.
Highlights
The striatum is the primary gateway for cortical inputs to the basal ganglia, in order to understand how inputs from the cortex to the basal ganglia influence behavior the characteristics of the corticostriatal projections must be understood
Even more surprising is the statistic that the likelihood of overlap between cortical inputs to adjacent striatal neurons is less than 10%
That estimate derives from calculations on corticostriatal organotypic cultures (Blackwell et al, 2003) but up to one-half of the depolarization might derive from GABA inputs rather than from cortical synapses
Summary
Anatomical considerations suggest massive cortical convergence on striatal neurons. Both Kincaid et al (1998) and ourselves (Wickens and Arbuthnott, 2010) estimate that about 5,000 cortical neurons might have synaptic contact with a single striatal neuron. Each cortical neuron of the 5,000 might only make one synapse on the striatal target neuron. Even more surprising is the statistic that the likelihood of overlap between cortical inputs to adjacent striatal neurons is less than 10%. The estimates of the number of cortical neurons likely to be needed to drive one striatal neuron suggest each input is so weak that almost 1,000 synapses must be coactivated to cause firing of a medium spiny neuron. That estimate derives from calculations on corticostriatal organotypic cultures (Blackwell et al, 2003) but up to one-half of the depolarization might derive from GABA inputs rather than from cortical synapses
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