Welcome back to our tutorial on the cerebellum. And in this part, I'd like to take a closer look at the circuitry of the cerebellum. And my learning objectives for you, are that I want you to be able to make a sketch, of the major inputs and outputs of the cerebellum. So, as all sketchers that I encourage you to make, the bigger the better. As you're making your sketch, I want you to be able to have a discussion. perhaps with a friend, a family member. Maybe someone who's taking the course along with you. But have a discussion. Even if it's just to hear the sound of your own voice. I would encourage you to describe the circuitry, that's involved in the processing that runs through the cerebellum. And as I'd like to describe for you, we can conceptualize this circuitry as involving a main excitatory loop that runs through the deep nuclei of the cerebellum. And then an inhibitory side loop, that runs up through the cortex and then back down to the deep cerebella nuclei. Before output leaves the cerebellum to influence circuits of upper motor neurons. Well, before we talk in detail about those circuits. I want to give you just a broad overview of the inputs to the cerebellum, and then talk just a little bit about function. So, the main inputs for the cerebellum come from a couple of different sources. they come from the pontine nuclei. These would account for the majority of the inputs to the cerebellum.. And notice the relationship of the pons to the cerebellum. The input from the pontine nuclei crosses the midline of the brain stem and projects into the contralateral hemisphere of the cerebellum. And the pathway by which it crosses the midline and enters the cerebellum, is the middle cerebellar peduncle. Now, notice that these pontine nuclei are in turn supplied by inputs that are derived from the cerebral cortex. So, the cerebral cortex then has the means by which it can send signals into the cerebellum, but only indirectly, through a replay in the pons. And as we discussed in the opening to the first part of this tutorial, one important function of the cerebellum, is to integrate executive commands about how we intend to move our body. Well, this is how this happens. Through input from the cortex to the pontine nuclei that are at the base of the pons, there's a synaptic connection. And then a relay from the base of the pons into the contralateral cerebellum. And notice that the input is being distributed both to the cortex of the cerebellum as well as to its deep nuclei. Well that's one massive and very important source of input to the cerebellum. Another important source of input to the cerebellum comes from our sensory systems, and specifically, from our proprioceptive systems, concerning the movements of our arms and legs. And this is fed into the cerebellum, via relays from the spinal cord in the caudal part of the medulla. And then there are inputs concerning the movements of our head. And these are conveyed into the cerebellum via the vestibular nuclei of the dorsal lateral tegmentum of the upper medulla and the caudal pons. And at least for some ganglion cells in the vestibular division of the eighth nerve, there may be direct connections from the eighth cranial nerve into the Cerebellum. So the cerebellum is getting this very important sensory feedback about how we're moving our bodies with respect to spinal cord inputs. And then, how our head is moving through three dimensional space. Well, there's a third major source of input to the cerebellum that I want to mention. And it's coming from a really fascinating nucleus of the ventral, and, somewhat intermediate aspect of the medulla. It's called the inferior olive, or the inferior olivary nucleus. This nucleus sends axons across the midline, then into the cerebellum from below, via the inferior cerebella peduncle. And the inferior olive is providing a learning signal for the cerebellum, and we're, we'll, we will talk about this in some detail. But, essentially, what this signal is doing is, it's conveying to the cerebellar cortex a time for synaptic change. And this synaptic plasticity appears to be the cellular and synaptic basis for motor learning in the cerebellum. Now, this inferior olive, in turn, is getting inputs that are descending from a pathway derived from the cerebral cortex. And the relay in this pathway is the red nucleus. So notice that the cortex is sending it's executive signals into the cerebellum via relay in the pons. But it's also informing the red nucleus, which is in turn activating the inferior olive. And when the inferior olive is active, now the cerebellum will engage in synaptic plasticity. And we think produce an error correction signal that can improve performance. Now, let me say just a few more words about the organization of these inputs, before we look at a more fine grain level at the organization of the circuits in the cerebellum. So, we have some anatomical terms that I want to define for you. they reflect the names the anatomists have given to the appearance of the inputs that we see under the microscope when we look at the cerebellum, at the cortex and at the deep nuclei. What we see when we look at the inputs that are coming from the pons, and those that are coming from the spinal cord and the vestibular nuclei. What we see is a morphological appearance of the input that we call the mossy fibers. So these inputs give rise to what we call mossy fibers, and this is now a bit of a shorthand term to describe all of this afferent input that is converging on the circuitry of the cerebellum. All except for one, very special kind of input, and that is the input that's coming from the inferior olive. This one type of input we call the climing fiber, and the reason we call it the climbing fiber should be obvious in just a few minutes. It has to do with the intimate relationship of the axons of this inferior olivary neuron, with respect to the principle cell type that we find in the cortex of the cerebellum. Now let me emphasize that both the mossy fibers and the climbing fibers, terminate at both levels of cerebellar processing, in the cerebellar cortex, and also in the deep nuclei. Now perhaps, it will be helpful just to remind you a bit of the inputs, to the cerebellum with a little bit more detail. you will recall that the inputs to the cerebellum from the spinal cord, convey signals about the movements of our body that are sensed by our preparative receptors. And they are conveyed the pathways that serve the lower extremities and the upper extremities. The pathway that serves the lower extremity involves a relay in the dorsal nucleus of Clarke, which is found in the thoracic segments of the spinal cord. The dorsal nucleus of Clarke grows an axon, that runs up the dorsal lateral white matter of the spinal cord and forms a tract that we call the dorsal spinal cerebellar tract. This is the major relay of proprioceptive signals from the lower extremities into the cerebellum. This pathway runs on the ipsilateral side of the cerebellum and the spinal cord. So the cerebellum is getting information about the movements of the ipsilateral side of the body. the same is true for the upper extremity, and this pathway runs from the first order neuron in the spinal nerves that enter the dorsal column. And then there's a synapse in the external cuneate nucleus the most lateral of our dorsal column nuclei. And from there the second order neuron projects, into the cerebellum via the inferior cerebellar peduncle in parallel with that dorsal-spinal cerebellar tract. And the cuneocerebellar tract is now involved with conveying proprioceptive signals about the movements of the upper extremities, into the cerebellum. So that's what we find here in the input from the spinal cord. So this input from the spinal cord is going be directed again, mainly at that, median zone of the cerebellum that we call the spinal cerebellum. The cerebral cerebellum on the other hand, is going to get information that is principally relayed via these pontine nuclei. So this massive connection from cortex to pontine nuclei to cerebellum is mainly going into the lateral hemispheres, into that region that we call the cerebral cerebellum. And then these vestibular inputs, that are being sent in some cases directly from the eighth nerve into the cerebellum. And others in a relay through the vestibular nuclei of the brain stem. these are being conveyed to the vestibular cerebellum, that flocculonodular lobe that's tucked underneath the posterior part of the cerebellum. One final point to make about the organization of the circuitry that should have been evident to you as we've been talking about it. And that is that the cerebellum is representing the ipsilateral side of the body. So perhaps I'm belaboring this point just a bit, but it certainly is worth some added emphasis. perhaps the spinal cord is what first sets up this ipsilateral representation by virtue of it's Ipsilateral dorsal spinal cerebellar pathway, that runs in via the inferior cerebellar peduncle. But, this principle of ipsilateral presentation in the cerebellum creates a bit of a problem, does it not? Because you now understand, that when it comes to the cerebral hemispheres, the principle is contralateral representation. So this means that, one side of the body is going to be represented in the opposite cerebral hemisphere, but in the same sided cerebellar hemisphere. And perhaps this provides a helpful way to just think through the necessity of this connection from cortex to pons, and then from pons to cerebellum. This will also be a challenge when think about the outputs of the cerebellum. That provide a means by which the cerebellar hemisphere on one side of the midline, can relate to circuits of upper motor neurons on the opposite side. So we'll face that challenge when we see an analogous figure that will be illustrating the output pathways of the cerebellum. But with respect to input, we can see how the spinal cord seems to set up this ipsilateral representation. And then the relay from the cortex meets the appropriate constraints, allowing one side of the cerebrum to interact with the appropriate hemisphere of the cerebellum.
