Mapping the macaque superior temporal sulcus: functional delineation of vergence and version eye-movement-related activity.

It is currently thought that the primate oculomotor system has evolved distinct but interrelated subsystems to generate different types of visually guided eye movements (e.g., saccades/smooth pursuit/vergence). Although progress has been made in elucidating the neural basis of these movement types, no study to date has investigated all three movement types on a large scale and within the same animals. Here, we used fMRI in rhesus macaque monkeys to map the superior temporal sulcus (STS) for BOLD modulation associated with visually guided eye movements. Further, we ascertained whether modulation in a given area was movement type specific and, if not, the modulation each movement type elicited relative to the others (i.e., dominance). Our results show that multiple areas within STS modulate during all movement types studied, including the middle temporal, medial superior temporal, fundus of the superior temporal, lower superior temporal, and dorsal posterior inferotemporal areas. Our results also reveal an area in dorsomedial STS that is modulated almost exclusively by vergence movements. In contrast, we found that ventrolateral STS is driven preferentially during versional movements. These results illuminate an STS network involved in processes associated with multiple eye movement types, illustrate unique patterns of modulation within said network as a function of movement type, and provide evidence for a vergence-specific area within dorsomedial STS. We conclude that producing categorically different eye movement types requires access to a common STS network and that individual network nodes are recruited differentially based upon the type of movement generated.

Sympathetic sprouting drives hippocampal cholinergic reinnervation that prevents loss of a muscarinic receptor-dependent long-term depression at CA3-CA1 synapses.

Degeneration of septohippocampal cholinergic neurons results in memory deficits attributable to loss of cholinergic modulation of hippocampal synaptic circuits. A remarkable consequence of cholinergic degeneration is the sprouting of noradrenergic sympathetic fibers from the superior cervical ganglia into hippocampus. The functional impact of sympathetic ingrowth on synaptic physiology has never been investigated. Here, we report that, at CA3-CA1 synapses, a Hebbian form of long-term depression (LTD) induced by muscarinic M1 receptor activation (mLTD) is lost after medial septal lesion. Unexpectedly, expression of mLTD is rescued by sympathetic sprouting. These effects are specific because LTP and other forms of LTD are unaffected. The rescue of mLTD expression is coupled temporally with the reappearance of cholinergic fibers in hippocampus, as assessed by the immunostaining of fibers for VAChT (vesicular acetylcholine transporter). Both the cholinergic reinnervation and mLTD rescue are prevented by bilateral superior cervical ganglionectomy, which also prevents the noradrenergic sympathetic sprouting. The new cholinergic fibers likely originate from the superior cervical ganglia because unilateral ganglionectomy, performed when cholinergic reinnervation is well established, removes the reinnervation on the ipsilateral side. Thus, the temporal coupling of the cholinergic reinnervation with mLTD rescue, together with the absence of reinnervation and mLTD expression after ganglionectomy, demonstrate that the autonomic-driven cholinergic reinnervation is essential for maintaining mLTD after central cholinergic cell death. We have discovered a novel phenomenon whereby the autonomic and central nervous systems experience structural rearrangement to replace lost cholinergic innervation in hippocampus, with the consequence of preserving a form of LTD that would otherwise be lost as a result of cholinergic degeneration.

Developing functional magnetic resonance imaging techniques for alert macaque monkeys.

Functional magnetic resonance imaging (fMRI) has developed rapidly into a major non-invasive tool for studying the human brain. However, due to a variety of technical difficulties, it has yet to be widely adopted for use in alert, trained non-human primates. Our laboratory has been developing techniques for such fMRI studies. As background, we first consider basic principles of fMRI imaging, experimental design, and post-processing. We discuss appropriate MRI system hardware and components for conducting fMRI studies in alert macaques, and the animal preparation and behavior necessary for optimal experiments. Finally, we consider alternative fMRI techniques using exogenous contrast agents, arterial spin labeling, and more direct measures of neural activation.