The Hippocampus

Synaptic Inputs to Mossy Cells

Our interests in the hippocampus are focused on mossy cells, the principal cell type in the dentate hilus. These glutamatergic neurons receive strong excitatory synaptic input from dentate granule cells, whose axons unfortunately are called mossy fibers. These axons generate extensive collaterals within the hilus, innervating both mossy cells and local hilar interneurons, as they project to CA3 pyramidal cells. Connections from granule cells to mossy cells are easily identified morphologically by the presence of thorny excrescences along the somata and proximal dendrites of mossy cells. Distal dendrites have conventional spines; the source of these inputs has not well established. Mossy cells project back to granule cells in the contralateral dentate gyrus and distant ipsilateral lamella. Mossy cells also generate some axonal connections to granule cells in their own lamella. Hilar mossy cells are often lost in people with temporal lobe epilepsy associated and in some animal model of epilepsy.

One of the most unusual aspects of mossy cell physiology is the high frequency of spontaneous synaptic inputs that constantly impinge on these neurons, both in vivo and in acute brain slices. This is surprising because granule cells, the most likely source of these excitatory inputs, are generally quiescent in vitro and have a very hyperpolarized resting membrane potential. We are currently exploring whether the spontaneous synaptic activity recorded in mossy cells arises from a subpopulation of active granule cells, ectopic activity in the axon terminals of granule cells, or from another class of local circuit neurons. We also showed that brief depolarization of mossy cells can lead to a transient potentiation of these excitatory synaptic inputs. This potentiation persists in tetrodotoxin and is associated with an increased frequency of miniature excitatory postsynaptic potentials, suggesting that a retrograde messenger may underlie this effect. 

Synchronous Discharges without Action Potentials

We have recently found an unusual form of synchronized activity in the hippocampus that does not require fast (sodium-based) action potentials. Most in vitro models that generate synchronous discharges in large populations of neurons in the hippocampus (disinhibition, low Mg, 4-AP) require propagation of impulses through axons; presumably to activate recurrent excitatory connections between CA3 pyramidal cells. Population activity always is suppressed by tetrodotoxin in these models. We recently found that TTX-resistant population discharges are generated spontaneously upon blockade of several classes of potassium channels with TEA and 4-AP. TTX-resistant discharges rely on conventional excitatory synaptic connections as this activity is blocked by AMPA receptor antagonists. We are currently exploring the synaptic mechanism underlying these events.

Related Publications

Williams PA, Larimer P, Gao Y and Strowbridge BW (2007) Semilunar granule cells: glutamatergic neurons in the rat dentate gyrus with axon collaterals in the inner molecular layer. J Neurosci 27:13756-13761.  PubMed

Frazier CJ, Strowbridge BW and Papke RL (2003) Nicotinic receptors on local circuit neurons in dentate gyrus: a potential role in regulation of granule cell excitability. J Neurophysiol 89:3018-3028.  PubMed

Strowbridge, B.W. (1999) Glutamate receptors mediate TTX-resistant synchronous activity in the rat hippocampus. J. Neurosci. 19:5758-5767.  Download PDF

Strowbridge, B.W. and Schwartzkroin, P.A. (1996) Transient potentiation of spontaneous EPSPs in rat mossy cells induced by depolarisation of a single neurone. J. Physiol. (Lond.) 494:493-510.

Buckmaster, P.S., Strowbridge, B.W., and Schwartzkroin, P.A. (1993) A Comparison of rat hippocampal mossy cells and CA3c pyramidal cells. J. Neurophysiol., 70:1281-1299.  

Strowbridge, B.W., Buckmaster, P.S., and Schwartzkroin, P.A. (1992) Potentiation of spontaneous synaptic activity in rat mossy cells. Neurosci. Lett. 142:205-210.  

Buckmaster P.S., Strowbridge, B.W., Kunkel, D.D., Schmiege, D.L., and Schwartzkroin, P.A. (1992) Mossy cell axonal projections to the dentate gyrus molecular layer in the rat hippocampal slice. Hippocampus 2:349-362.