Biomedical subjects

Jason N MacLean

Publications and source records attributed to Jason N MacLean.

5 recordsLinked to original sources

PubMed2006

A visual thalamocortical slice.

We describe a thalamocortical slice preparation in which connectivity between the mouse lateral geniculate nucleus (LGN) and primary visual cortex (V1) is preserved. Through DiI injections in fixed brains we traced and created a three-dimensional model of the mouse visual pathways. From this computer model we designed a slice preparation that contains a projection from LGN to V1. We prepared brain slices with these predicted coordinates and demonstrated anatomical LGN-V1 connectivity in these slices after LGN tracer injections. We also revealed functional LGN-V1 connectivity by stimulating LGN electrically and detecting responses in layer 4 of V1 using calcium imaging, field potential recordings and whole-cell recordings. We also identified layer-4 neurons that receive direct thalamocortical input. Finally, we compared cortical activity after LGN stimulation with spontaneous cortical activity and found significant overlap of the spatiotemporal dynamics generated by both types of events.

Animals↗

PubMed2005

Internal dynamics determine the cortical response to thalamic stimulation.

Although spontaneous activity occurs throughout the neocortex, its relation to the activity produced by external or sensory inputs remains unclear. To address this, we used calcium imaging of mouse thalamocortical slices to reconstruct, with single-cell resolution, the spatiotemporal dynamics of activity of layer 4 in the presence or absence of thalamic stimulation. We found spontaneous neuronal coactivations corresponded to intracellular UP states. Thalamic stimulation of sufficient frequency (>10 Hz) triggered cortical activity, and UP states, indistinguishable from those arising spontaneously. Moreover, neurons were activated in identical and precise spatiotemporal patterns in thalamically triggered and spontaneous events. The similarities between cortical activations indicate that intracortical connectivity plays the dominant role in the cortical response to thalamic inputs. Our data demonstrate that precise spatiotemporal activity patterns can be triggered by thalamic inputs and indicate that the thalamus serves to release intrinsic cortical dynamics.

Animals↗

PubMed2005

Activity-independent coregulation of IA and Ih in rhythmically active neurons.

The fast transient potassium or A current (IA) plays an important role in determining the activity of central pattern generator neurons. We have previously shown that the shal K+ channel gene encodes IA in neurons of the pyloric network in the spiny lobster. To further study how IA shapes pyloric neuron and network activity, we microinjected RNA for a shal-GFP fusion protein into four identified pyloric neuron types. Neurons expressing shal-GFP had a constant increase in IA amplitude, regardless of cell type. This increase in IA was paralleled by a concomitant increase in the hyperpolarization-activated cation current Ih in all pyloric neurons. Despite significant increases in these currents, only modest changes in cell firing properties were observed. We used models to test two hypotheses to explain this failure to change firing properties. First, this may reflect the mislocalization of the expressed shal protein solely to the somata and initial neurites of injected neurons, rendering it electrically remote from the integrating region in the neuropil. To test this hypothesis, we generated a multicompartment model where increases in IA could be localized to the soma, initial neurite, or neuropil/axon compartments. Although spike activity was somewhat more sensitive to increases in neuropil/axon versus somatic/primary neurite IA, increases in IA limited to the soma and primary neurite still evoked much more dramatic changes than were seen in the shal-GFP-injected neurons. Second, the effect of the increased IA could be compensated by the endogenous increase in Ih. To test this, we modeled the compensatory increases of IA and Ih with a cycling two-cell model. We found that the increase in Ih was sufficient to compensate the effects of increased IA, provided that they increase in a constant ratio, as we observed experimentally in both shal-injected and noninjected neurons. Thus an activity-independent homeostatic mechanism maintains constant neuronal activity in the face of dramatic increases in IA.

Action Potentials↗

PubMed2005

The cortex as a central pattern generator.

Vertebrate spinal cord and brainstem central pattern generator (CPG) circuits share profound similarities with neocortical circuits. CPGs can produce meaningful functional output in the absence of sensory inputs. Neocortical circuits could be considered analogous to CPGs as they have rich spontaneous dynamics that, similar to CPGs, are powerfully modulated or engaged by sensory inputs, but can also generate output in their absence. We find compelling evidence for this argument at the anatomical, biophysical, developmental, dynamic and pathological levels of analysis. Although it is possible that cortical circuits are particularly plastic types of CPG ('learning CPGs'), we argue that present knowledge about CPGs is likely to foretell the basic principles of the organization and dynamic function of cortical circuits.

Animals↗

PubMed2003

Activity-independent homeostasis in rhythmically active neurons.

The shal gene encodes the transient potassium current (I(A)) in neurons of the lobster stomatogastric ganglion. Overexpression of Shal by RNA injection into neurons produces a large increase in I(A), but surprisingly little change in the neuron's firing properties. Accompanying the increase in I(A) is a dramatic and linearly correlated increase in the hyperpolarization-activated inward current (I(h)). The enhanced I(h) electrophysiologically compensates for the enhanced I(A), since pharmacological blockade of I(h) uncovers the physiological effects of the increased I(A). Expression of a nonfunctional mutant Shal also induces a large increase in I(h), demonstrating a novel activity-independent coupling between the Shal protein and I(h) enhancement. Since I(A) and I(h) influence neuronal activity in opposite directions, our results suggest a selective coregulation of these channels as a mechanism for constraining cell activity within appropriate physiological parameters.

Action Potentials↗