Nikolai C. Dembrow

Projection-Specific Neuromodulation of Medial Prefrontal Cortex Neurons

Mnemonic persistent activity in the prefrontal cortex (PFC) constitutes the neural basis of working memory. To understand how neuromodulators contribute to the generation of persistent activity, it is necessary to identify the intrinsic properties of the layer V pyramidal neurons that transfer this information to downstream networks. Here we show that the somatic dynamic and integrative properties of layer V pyramidal neurons in the rat medial PFC depend on whether they project subcortically to the pons [corticopontine (CPn)] or to the contralateral cortex [commissural (COM)]. CPn neurons display low temporal summation and accelerate in firing frequency when depolarized, whereas COM neurons have high temporal summation and display spike frequency accommodation. In response to dynamic stimuli, COM neurons act as low-pass filters, whereas CPn neurons act as bandpass filters, resonating in the theta frequency range (3–6 Hz). The disparate subthreshold properties of COM and CPn neurons can be accounted for by differences in the hyperpolarization-activated cyclic nucleotide gated cation h-current. Interestingly, neuromodulators hypothesized to enhance mnemonic persistent activity affect COM and CPn neurons distinctly. Adrenergic modulation shifts the dynamic properties of CPn but not COM neurons and increases the excitability of CPn neurons significantly more than COM neurons. In response to cholinergic modulation, CPn neurons were much more likely to display activity-dependent intrinsic persistent firing than COM neurons. Together, these data suggest that the two categories of projection neurons may subserve separate functions in PFC and may be engaged differently during working memory processes.

A specific synaptic pathway activates a conditional plateau potential underlying protraction phase in the Aplysia feeding central pattern generator

A common feature in the architecture of neuronal networks is a high degree of seemingly redundant synaptic connectivity. In many cases, the synaptic inputs converging on any particular neuron all use the same neurotransmitter and appear to be fundamentally equivalent. Here, we analyze a striking counterexample in which such inputs are not equivalent and, as a result, play very different roles in the generation of the pattern of activity produced by the network. In the feeding central pattern generator of Aplysia, the pattern-initiating neuron B50 elicits motor programs by exciting the plateauing neuron B31/B32 in two ways: directly and indirectly through neuron B63. All of the synaptic connections use ACh. Despite the direct input of B50 to B31/B32, the indirect pathway of exciting B31/B32 through B63 is required for B50 to elicit the B31/B32 plateau potential and the motor program. We dissect this requirement using the muscarinic cholinergic antagonist pirenzepine. Pirenzepine blocks the B50-elicited motor program, the plateau potential in B31/B32, and, notably, a slow component of the EPSP elicited in B31/B32 by B63 but not that elicited by B50. The muscarinic agonist oxotremorine restores the plateau potential in B31/B32 and eliminates the necessity for B63 in B50-elicited motor programs. Together, our analysis shows that the plateau potential in B31/B32 is not endogenous but conditional, furthermore conditional on one particular synaptic input, that from B63. Thus, among several inputs to B31/B32 that use the same transmitter, the input from B63 is functionally distinct in its preferential access to the plateau potential that represents the committed step toward the initiation of a motor program.

Cerebrin prohormone processing, distribution and action in Aplysia californica

The isolation, characterization, and bioactivity in the feeding circuitry of a novel neuropeptide in the Aplysia californica central nervous system are reported. The 17‐residue amidated peptide, NGGTADALYNLPDLEKIamide, has been termed cerebrin due to its primary location in the cerebral ganglion. Liquid chromatographic purification guided by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry allowed the isolation of the peptide with purity adequate for Edman sequencing. The cerebrin cDNA has been characterized and encodes an 86 amino acid prohormone that predicts cerebrin and one additional peptide. Mapping using in situ hybridization and immunocytochemistry showed that cerebrin containing neuronal somata are localized almost exclusively in the cerebral ganglion, mostly in the F‐ and C‐clusters. Both immunostaining and mass spectrometry demonstrated the presence of cerebrin in the neurohemal region of the upper labial nerve. In addition, immunoreactive processes were detected in the neuropil of all of the ganglia, including the buccal ganglia, and in some interganglionic connectives, including the cerebral‐buccal connective. This suggests that cerebrin may also function as a local signaling molecule. Cerebrin has a profound effect on the feeding motor pattern elicited by the command‐like neuron CBI‐2, dramatically shortening the duration of the radula protraction in a concentration‐dependent manner, mimicking the motor‐pattern alterations observed in food induced arousal states. These findings suggest that cerebrin may contribute to food‐induced arousal in the animal. Cerebrin‐like immunoreactivity is also present in Lymnaea stagnalis suggesting that cerebrin‐like peptides may be widespread throughout gastropoda.

Calcium Dynamics Encode the Magnitude of a Graded Memory Underlying Sensorimotor Adaptation

The role of Ca(2+) in the induction of neural correlates of memory has frequently been described in binary terms despite the fact that many forms of memory are graded in their strength and/or persistence. We find that Ca(2+) dynamics encode the magnitude of sensorimotor adaptation of the electromotor output in a weakly electric fish. The neural correlate of this memory is a synaptically induced Ca(2+)-dependent enhancement of intrinsic excitability of neurons responsible for setting the electromotor output. Changes in Ca(2+) during induction accurately predict the magnitude of this graded memory over a wide range of stimuli. Thus despite operating over a range from seconds to tens of minutes, the encoding of graded memory can be mediated by a relatively simple cellular mechanism.